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B cell phenotype, activity, and function in idiopathic nephrotic syndrome

Pediatric Research volume 93, pages 1828–1836 (2023)Cite this article

Abstract

Idiopathic nephrotic syndrome (INS) is the most frequent glomerular disease in childhood. However, its underlying etiology mechanism lacks thorough understanding. Previous studies have described INS as a T cell functional disorder resulting in increased plasma lymphocyte-derived permeability factors. In children with frequent relapses of nephrotic syndrome, the mechanism underlying the therapeutic efficacy of CD20 monoclonal antibodies in depleting B cells may provide additional evidence in exploring the critical role of B lymphocytes in INS pathogenesis. Previous studies have proposed that RTX bound to CD20 through antibody-dependent and complement-dependent cytotoxicity and led to lytic clearance of B cells. Additionally, RTX exerted an effect by blocking the interaction between B and T cells or regulating homeostasis and functions of T cell subsets. Recent studies on the development, differentiation, and activation of B-lymphocytes in glomerular diseases have suggested that the B-lymphocytes participate in the INS pathogenesis through interaction with T cells, secretion of antibodies, or production of cytokines. In this study, we aimed to provide a detailed description of the current knowledge on the development, differentiation, activity, functions, and related regulating factors of B cells involved in INS. Thus, further understanding of the immunopathogenesis of INS may offer some opportunities in precisely targeting B cells during therapeutic interventions.

Impact

  • The topic “B cells play a role in glomerular disease” is a novel point, which is not completely described previously.

  • We described interactions between T and B cells and immunoglobulin, IgG, IgM, IgE, etc. as well in glomerular disease.

  • The research of regulatory factors associated with B cell’s function, like BAFF, is a hot topic in other diseases; however, it is rare in glomerular disease.

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Fig. 1: Different stages of B cells in the bone marrow and peripheral tissues.
Fig. 2: The possible role of B lymphocytes during the onset of INS.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Sahali, D. et al. Immunopathogenesis of idiopathic nephrotic syndrome with relapse. Semin. Immunopathol. 36, 421–429 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Noone, D. G., Iijima, K. & Parekh, R. Idiopathic nephrotic syndrome in children. Lancet 392, 61–74 (2018).

    Article  PubMed  Google Scholar 

  3. Shalhoub, R. J. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2, 556–560 (1974).

    Article  CAS  PubMed  Google Scholar 

  4. Davin, J. C. The glomerular permeability factors in idiopathic nephrotic syndrome. Pediatr. Nephrol. 31, 207–215 (2016).

    Article  PubMed  Google Scholar 

  5. Eddy, A. A. & Symons, J. M. Nephrotic syndrome in childhood. Lancet 362, 629–639 (2003).

    Article  PubMed  Google Scholar 

  6. Takei, T. & Nitta, K. Rituximab and minimal change nephrotic syndrome: a therapeutic option. Clin. Exp. Nephrol. 15, 641–647 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. Ravani, P., Bonanni, A., Rossi, R., Caridi, G. & Ghiggeri, G. M. Anti-CD20 antibodies for idiopathic nephrotic syndrome in children. Clin. J. Am. Soc. Nephrol. 11, 710–720 (2016).

    Article  CAS  PubMed  Google Scholar 

  8. Kemper, M. J., Zepf, K., Klaassen, I., Link, A. & Muller-Wiefel, D. E. Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am. J. Nephrol. 25, 132–137 (2005).

    Article  PubMed  Google Scholar 

  9. Ye, Q. & Mao, J. H. Immunologic pathogenesis of idiopathic nephrotic syndrome in children: the present and future. Zhonghua Er Ke Za Zhi 58, 705–707 (2020).

    CAS  PubMed  Google Scholar 

  10. Somlo, S. & Mundel, P. Getting a foothold in nephrotic syndrome. Nat. Genet. 24, 333–335 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Lorenzo, H. K. & Candelier, J. J. Syndrome néphrotique idiopathique et facteurs circulants - une arlésienne? [Idiopathic nephrotic syndrome: une Arlésienne?]. Med. Sci. 35, 659–666 (2019).

    Google Scholar 

  12. Allman, D. M., Ferguson, S. E., Lentz, V. M. & Cancro, M. P. Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells. J. Immunol. 151, 4431–4444 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. Wang, Y., Liu, J., Burrows, P. D. & Wang, J. Y. B cell development and maturation. Adv. Exp. Med. Biol. 1254, 1–22 (2020).

    Article  CAS  PubMed  Google Scholar 

  14. Allman, D. & Pillai, S. Peripheral B cell subsets. Curr. Opin. Immunol. 20, 149–157 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ribatti, D. The discovery of plasma cells: an historical note. Immunol. Lett. 188, 64–67 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Colucci, M., Corpetti, G., Emma, F. & Vivarelli, M. Immunology of idiopathic nephrotic syndrome. Pediatr. Nephrol. 33, 573–584 (2018).

    Article  PubMed  Google Scholar 

  17. Carsetti, R., Rosado, M. M. & Wardmann, H. Peripheral development of B cells in mouse and man. Immunol. Rev. 197, 179–191 (2004).

    Article  PubMed  Google Scholar 

  18. Hoffman, W., Lakkis, F. G. & Chalasani, G. B cells, antibodies, and more. Clin. J. Am. Soc. Nephrol. 11, 137–154 (2016).

    Article  CAS  PubMed  Google Scholar 

  19. Barratt-Boyes, S. M. Comparative immunology, microbiology and infectious diseases. Introduction. Comp. Immunol. Microbiol. Infect. Dis. 35, 217–218 (2012).

    Article  PubMed  Google Scholar 

  20. Inoue, T., Moran, I., Shinnakasu, R., Phan, T. G. & Kurosaki, T. Generation of memory B cells and their reactivation. Immunol. Rev. 283, 138–149 (2018).

    Article  CAS  PubMed  Google Scholar 

  21. Alachkar, H., Taubenheim, N., Haeney, M. R., Durandy, A. & Arkwright, P. D. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin. Immunol. 120, 310–318 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Vodjgani, M. et al. Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications. J. Investig. Allergol. Clin. Immunol. 17, 321–328 (2007).

    CAS  PubMed  Google Scholar 

  23. Lin, L. et al. Consolidation treatment and long-term prognosis of rituximab in minimal change disease and focal segmental glomerular sclerosis. Drug Des. Dev. Ther. 15, 1945–1953 (2021).

    Article  Google Scholar 

  24. Hansrivijit, P., Cheungpasitporn, W., Thongprayoon, C. & Ghahramani, N. Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis. BMC Nephrol. 21, 134 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kronbichler, A. et al. Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis: a systematic review. Am. J. Nephrol. 39, 322–330 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Chan, E. Y. et al. Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes. Kidney Int. 97, 393–401 (2020).

    Article  CAS  PubMed  Google Scholar 

  27. Hofmann, K., Clauder, A. K. & Manz, R. A. Targeting B cells and plasma cells in autoimmune diseases. Front. Immunol. 9, 835 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Cara-Fuentes, G. et al. Rituximab in idiopathic nephrotic syndrome: does it make sense? Pediatr. Nephrol. 29, 1313–1319 (2014).

    Article  PubMed  Google Scholar 

  29. Stroopinsky, D., Katz, T., Rowe, J. M., Melamed, D. & Avivi, I. Rituximab-induced direct inhibition of T-cell activation. Cancer Immunol. Immunother. 61, 1233–1241 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Suyama, K. et al. Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis. Pediatr. Int. 58, 219–223 (2016).

    Article  CAS  PubMed  Google Scholar 

  31. Bhatia, D. et al. Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome. Pediatr. Res. 84, 520–526 (2018).

    Article  CAS  PubMed  Google Scholar 

  32. Leandro, M. J., Cambridge, G., Ehrenstein, M. R. & Edwards, J. C. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 54, 613–620 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Fornoni, A. et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci. Transl. Med. 3, 85ra46 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Takahashi, Y., Ikezumi, Y. & Saitoh, A. Rituximab protects podocytes and exerts anti-proteinuric effects in rat adriamycin-induced nephropathy independent of B-lymphocytes. Nephrology 22, 49–57 (2017).

    Article  CAS  PubMed  Google Scholar 

  35. Hua, Z. & Hou, B. TLR signaling in B-cell development and activation. Cell Mol. Immunol. 10, 103–106 (2013).

    Article  CAS  PubMed  Google Scholar 

  36. Thorley-Lawson, D. A. EBV persistence-introducing the virus. Curr. Top. Microbiol. Immunol. 390, 151–209 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lünemann, A., Rowe, M. & Nadal, D. Innate immune recognition of EBV. Curr. Top. Microbiol. Immunol. 391, 265–287 (2015).

    PubMed  Google Scholar 

  38. Houen, G. & Trier, N. H. Epstein-Barr virus and systemic autoimmune diseases. Front. Immunol. 11, 587380 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Dossier, C., Jamin, A. & Deschênes, G. Idiopathic nephrotic syndrome: the EBV hypothesis. Pediatr. Res. 81, 233–239 (2017).

    Article  PubMed  Google Scholar 

  40. Jamin, A. et al. Toll-like receptor 3 expression and function in childhood idiopathic nephrotic syndrome. Clin. Exp. Immunol. 182, 332–345 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Printza, N., Papachristou, F., Tzimouli, V., Taparkou, A. & Kanakoudi-Tsakalidou, F. Peripheral CD19+ B cells are increased in children with active steroid-sensitive nephrotic syndrome. NDT Plus 2, 435–436 (2009).

    PubMed  PubMed Central  Google Scholar 

  42. Yildiz, B., Cetin, N., Kural, N. & Colak, O. CD19 + CD23+ B cells, CD4 + CD25+ T cells, E-selectin and interleukin-12 levels in children with steroid sensitive nephrotic syndrome. Ital. J. Pediatr. 39, 42 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Colucci, M. et al. B cell reconstitution after rituximab treatment in idiopathic nephrotic syndrome. J. Am. Soc. Nephrol. 27, 1811–1822 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Colucci, M. et al. B cell phenotype in pediatric idiopathic nephrotic syndrome. Pediatr. Nephrol. 34, 177–181 (2019).

    Article  PubMed  Google Scholar 

  45. Yu, P. et al. Clinical significance of B lymphocyte phenotype in children with frequent-relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome. J. Practical Med. 36, 954–958 (2020) (in Chinese).

    Google Scholar 

  46. Ling, C. et al. Altered B-lymphocyte homeostasis in idiopathic nephrotic syndrome. Front. Pediatr. 7, 377 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Crickx, E. et al. Rituximab-resistant splenic memory B cells and newly engaged naïve B cells fuel relapses in patients with immune thrombocytopenia. Sci. Transl. Med. 13, eabc3961 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Santos, J. E. et al. Rituximab use in adult glomerulopathies and its rationale. J. Bras. Nefrol. 42, 77–93 (2020).

    Article  PubMed  Google Scholar 

  49. Dantal, J. et al. Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. J. Am. Soc. Nephrol. 9, 1709–1715 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Thurman, J. M. et al. Complement activation in patients with focal segmental glomerulosclerosis. PLoS ONE 10, e0136558 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Mirioglu, S. et al. Co-deposition of IgM and C3 may indicate unfavorable renal outcomes in adult patients with primary focal segmental glomerulosclerosis. Kidney Blood Press. Res. 44, 961–972 (2019).

    Article  CAS  PubMed  Google Scholar 

  52. Strassheim, D. et al. IgM contributes to glomerular injury in FSGS. J. Am. Soc. Nephrol. 24, 393–406 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Huang, J. et al. Complement activation profile of patients with primary focal segmental glomerulosclerosis. PLoS ONE 15, e0234934 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Chen, S., Wang, J. & Liang, S. Clinical significance of T lymphocyte subsets, immunoglobulin and complement expression in peripheral blood of children with steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome. Am. J. Transl. Res. 13, 1890–1895 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. El Mashad, G. M., El Hady Ibrahim, S. A. & Abdelnaby, S. A. A. Immunoglobulin G and M levels in childhood nephrotic syndrome: two centers Egyptian study. Electron Physician 9, 3728–3732 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Youssef, D. M., Salam, S. M. & Karam, R. A. Prediction of steroid response in nephrotic syndrome by humoral immunity assessment. Indian J. Nephrol. 21, 186–190 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ahmed, A. et al. Low serum IgG level during remission: a predictor of frequent relapse nephrotic syndrome. DS (Child) HJ 27, 64–67 (2011).

    Google Scholar 

  58. Yokoyama, H. et al. Impaired immunoglobulin G production in minimal change nephrotic syndrome in adults. Clin. Exp. Immunol. 70, 110–115 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Delbe-Bertin, L., Aoun, B., Tudorache, E., Lapillone, H. & Ulinski, T. Does rituximab induce hypogammaglobulinemia in patients with pediatric idiopathic nephrotic syndrome? Pediatr. Nephrol. 28, 447–451 (2013).

    Article  PubMed  Google Scholar 

  60. Yap, H. K. et al. The incidence of atopy in steroid-responsive nephrotic syndrome: Clinical and immunological parameters. Ann. Allergy 51, 590–594 (1983).

    CAS  PubMed  Google Scholar 

  61. Abdel-Hafez, M., Shimada, M., Lee, P. Y., Johnson, R. J. & Garin, E. H. Idiopathic nephrotic syndrome and atopy: is there a common link? Am. J. Kidney Dis. 54, 945–953 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kanai, T. et al. Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome. Clin. Exp. Nephrol. 14, 578–583 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Hsiao, C. C. et al. Immunoglobulin E and G levels in predicting minimal change disease before renal biopsy. Biomed. Res. Int. 2018, 3480309 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Musante, L. et al. Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome. Clin. Exp. Immunol. 141, 491–499 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jamin, A. et al. Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice. J. Autoimmun. 89, 149–161 (2018).

    Article  CAS  PubMed  Google Scholar 

  66. Watts, A. J. B. et al. Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology. J. Am. Soc. Nephrol. 33, 238–252 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hada, I. et al. A novel mouse model of idiopathic nephrotic syndrome induced by immunization with the podocyte protein Crb2. J. Am. Soc. Nephrol. https://doi.org/10.1681/ASN.2022010070 (2022).

  68. Chan, O. T., Hannum, L. G., Haberman, A. M., Madaio, M. P. & Shlomchik, M. J. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J. Exp. Med. 189, 1639–1648 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sfikakis, P. P. et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum. 52, 501–513 (2005).

    Article  CAS  PubMed  Google Scholar 

  70. Pescovitz, M. D. Rituximab, an anti-CD20 monoclonal antibody: History and mechanism of action. Am. J. Transpl. 6, 859–866 (2006).

    Article  CAS  Google Scholar 

  71. Hua, Z. & Hou, B. The role of B cell antigen presentation in the initiation of CD4+ T cell response. Immunol. Rev. 296, 24–35 (2020).

    Article  CAS  PubMed  Google Scholar 

  72. Alonso-Guallart, P. et al. CD40L-stimulated B cells for ex-vivo expansion of polyspecific non-human primate regulatory T cells for translational studies. Clin. Exp. Immunol. 203, 480–492 (2021).

    Article  CAS  PubMed  Google Scholar 

  73. Eroglu, F. K. et al. CD80 expression and infiltrating regulatory T cells in idiopathic nephrotic syndrome of childhood. Pediatr. Int. 61, 1250–1256 (2019).

    Article  CAS  PubMed  Google Scholar 

  74. Rowshanravan, B., Halliday, N. & Sansom, D. M. CTLA-4: a moving target in immunotherapy. Blood 131, 58–67 (2018).

    Article  CAS  PubMed  Google Scholar 

  75. Hackl, A. et al. The role of the immune system in idiopathic nephrotic syndrome. Mol. Cell Pediatr. 8, 18 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chebotareva, N., Bobkova, I. & Lysenko, L. T regulatory cells in renal tissue of patients with nephrotic syndrome. Pediatr. Int. 62, 884–885 (2020).

    Article  PubMed  Google Scholar 

  77. Tsuji, S. et al. Regulatory T cells and CTLA-4 in idiopathic nephrotic syndrome. Pediatr. Int. 59, 643–646 (2017).

    Article  CAS  PubMed  Google Scholar 

  78. Tunçay, S. C., Hakverdi, G., Şenol, Ö. & Mir, S. Regulatory T-cell changes in patients with steroid-resistant nephrotic syndrome after rituximab therapy. Saudi J. Kidney Dis. Transpl. 32, 1028–1033 (2021).

    Article  PubMed  Google Scholar 

  79. Guimarães, F. T. L. et al. T-lymphocyte-expressing inflammatory cytokines underlie persistence of proteinuria in children with idiopathic nephrotic syndrome. J. Pediatr. 94, 546–553 (2018).

    Article  Google Scholar 

  80. Liu, L. L. et al. Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome. Clin. Immunol. 139, 314–320 (2011).

    Article  CAS  PubMed  Google Scholar 

  81. Stangou, M. et al. Impact of Τh1 and Τh2 cytokines in the progression of idiopathic nephrotic syndrome due to focal segmental glomerulosclerosis and minimal change disease. J. Nephropathol. 6, 187–195 (2017).

    Article  PubMed  Google Scholar 

  82. Wang, R. et al. Effects of rituximab on T lymphocyte subsets and urinary CD80 levels in children with hormone-dependent nephrotic syndrome. J. Southeast Univ. (Med. Ed.) 40, 612–617 (2021) (in Chinese).

    Google Scholar 

  83. Fribourg, M. et al. CyTOF-enabled analysis identifies class-switched B cells as the main lymphocyte subset associated with disease relapse in children with idiopathic nephrotic syndrome. Front. Immunol. 12, 726428 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Watanabe, R. et al. Regulatory B cells (B 10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbares sysremic autoimmunity. J. Immunol. 184, 4801–4809 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Doublier, S. et al. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS. PLoS ONE 12, e0188045 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Pistoia, V. Production of cytokines by human B cells in health and disease. Immunol. Today 18, 343–350 (1997).

    Article  CAS  PubMed  Google Scholar 

  87. Oleinika, K., Mauri, C. & Salama, A. D. Effector and regulatory B cells in immune-mediated kidney disease. Nat. Rev. Nephrol. 15, 11–26 (2019).

    Article  CAS  PubMed  Google Scholar 

  88. Wang, L., Fu, Y. & Chu, Y. Regulatory B cells. Adv. Exp. Med. Biol. 1254, 87–103 (2020).

    Article  CAS  PubMed  Google Scholar 

  89. Yang, H. The Role and Mechanism of Regulatory B Cells in Th17/Treg Immune Imbalance in Children with Primary Nephrotic Syndrome (Chongqing Medical University, 2016).

  90. Matsushita, T. Regulatory and effector B cells: friends or foes? J. Dermatol. Sci. 93, 2–7 (2019).

    Article  CAS  PubMed  Google Scholar 

  91. Salsano, M. E. et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 96, 561–566 (2007).

    Article  PubMed  Google Scholar 

  92. Matsumoto, K., Ohi, H. & Kanmatsuse, K. Interleukin-4 cooperates with interleukin-10 to inhibit vascular permeability factor release by peripheral blood mononuclear cells from patients with minimal-change nephrotic syndrome. Am. J. Nephrol. 19, 21–27 (1999).

    Article  CAS  PubMed  Google Scholar 

  93. Zheng, Y., Hou, L., Wang, X. L., Zhao, C. G. & Du, Y. A review of nephrotic syndrome and atopic diseases in children. Transl. Androl. Urol. 10, 475–482 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Roca, N. et al. Activation of the acute inflammatory phase response in idiopathic nephrotic syndrome: association with clinicopathological phenotypes and with response to corticosteroids. Clin. Kidney J. 14, 1207–1215 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Prasad, N. et al. Differential alteration in peripheral T-regulatory and T-effector cells with change in P-glycoprotein expression in Childhood Nephrotic Syndrome: a longitudinal study. Cytokine 72, 190–196 (2015).

    Article  CAS  PubMed  Google Scholar 

  96. Shabgah, A. G., Shariati-Sarabi, Z., Tavakkol-Afshari, J. & Mohammadi, M. The role of BAFF and APRIL in rheumatoid arthritis. J. Cell Physiol. 234, 17050–17063 (2019).

    Article  CAS  PubMed  Google Scholar 

  97. Jackson, S. W. & Davidson, A. BAFF inhibition in SLE-Is tolerance restored? Immunol. Rev. 292, 102–119 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Möckel, T., Basta, F., Weinmann-Menke, J. & Schwarting, A. B cell activating factor (BAFF): structure, functions, autoimmunity and clinical implications in systemic lupus erythematosus (SLE). Autoimmun. Rev. 20, 102736 (2021).

    Article  PubMed  Google Scholar 

  99. Kaegi, C., Steiner, U. C., Wuest, B., Crowley, C. & Boyman, O. Systematic review of safety and efficacy of belimumab in treating immune-mediated disorders. Allergy 76, 2673–2683 (2021).

    Article  CAS  PubMed  Google Scholar 

  100. Matsushita, T. et al. BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance. Sci. Adv. 4, eaas9944 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Mackay, F., Schneider, P., Rennert, P. & Browning, J. BAFF AND APRIL: a tutorial on B cell survival. Annu. Rev. Immunol. 21, 231–264 (2003).

    Article  CAS  PubMed  Google Scholar 

  102. Weisel, F. & Shlomchik, M. Memory B cells of mice and humans. Annu. Rev. Immunol. 35, 255–284 (2017).

    Article  CAS  PubMed  Google Scholar 

  103. Müller-Winkler, J. et al. Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival. J. Exp. Med. 218, e20191393 (2021).

    Article  PubMed  Google Scholar 

  104. Bossen, C. & Schneider, P. BAFF, APRIL and their receptors: structure, function and signaling. Semin. Immunol. 18, 263–275 (2006).

    Article  CAS  PubMed  Google Scholar 

  105. Du, S. W., Jacobs, H. M., Arkatkar, T., Rawlings, D. J. & Jackson, S. W. Integrated B cell, Toll-like, and BAFF receptor signals promote autoantibody production by transitional B cells. J. Immunol. 201, 3258–3268 (2018).

    Article  CAS  PubMed  Google Scholar 

  106. Oniszczuk, J. et al. Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults. Nephrol. Dial. Transpl. 36, 609–617 (2021).

    Article  CAS  Google Scholar 

  107. Pranzatelli, M. R., Tate, E. D., Travelstead, A. L. & Verhulst, S. J. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS. Cytokine 53, 384–389 (2011).

    Article  CAS  PubMed  Google Scholar 

  108. Shi, J. et al. PD-1 controls follicular T helper cell positioning and function. Immunity 49, 264–274.e4 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Varricchi, G. et al. T follicular helper (TFH) cells in normal immune responses and in allergic disorders. Allergy 71, 1086–1094 (2016).

    Article  CAS  PubMed  Google Scholar 

  110. Crotty, S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29, 621–663 (2011).

    Article  CAS  PubMed  Google Scholar 

  111. Linterman, M. A. et al. Follicular helper T cells are required for systemic autoimmunity. J. Exp. Med. 206, 561–576 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhang, N. et al. A higher frequency of CD4+CXCR5+ T follicular helper cells in adult patients with minimal change disease. Biomed. Res. Int. 2014, 836157 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Li, T. et al. Increased PD-1+CD154+ TFH cells are possibly the most important functional subset of PD-1+ T follicular helper cells in adult patients with minimal change disease. Mol. Immunol. 94, 98–106 (2018).

    Article  CAS  PubMed  Google Scholar 

  114. Audia, S. et al. B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia. J. Autoimmun. 77, 89–95 (2017).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University, 221002, Xuzhou, Jiangsu, China

    Junhan Liu & Fengjun Guan

Authors
  1. Junhan Liu
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  2. Fengjun Guan
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Contributions

Conception and design: both authors; administrative support: F.G.; organization of literatures: J.L.; manuscript writing: both authors; final approval of manuscript: both authors.

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Correspondence to Fengjun Guan.

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Liu, J., Guan, F. B cell phenotype, activity, and function in idiopathic nephrotic syndrome. Pediatr Res 93, 1828–1836 (2023). https://doi.org/10.1038/s41390-022-02336-w

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