Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Innate B cell helpers reveal novel types of antibody responses

Nature Immunology volume 14, pages 119–126 (2013)Cite this article

Subjects

Abstract

Antibody responses are classified according to whether B cells receive help from T cells—that is, whether they are thymus-dependent (TD) responses or thymus-independent (TI) responses. The latter can be elicited by microbial ligands (TI type 1) or by extensive crosslinking of the B cell antigen receptor (BCR; TI type 2). The hallmark of a TD response is the induction of germinal centers in which follicular helper T cells (TFH cells) select B cells with somatically mutated high-affinity BCRs to become memory cells. Studies have shown that B cells can also receive innate TD help from natural killer T cells (NKT cells) and innate TI help from cells such as neutrophils but that the outcome of such help differs from conventional TD and TI responses. Here we update the classification of antibody responses to take into account these emerging types of B cell helpers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Updated classification of antibody responses.
Figure 2: TD antibody responses.
Figure 3: TI antibody responses.

Similar content being viewed by others

References

  1. MacLennan, I.C. Germinal centers. Annu. Rev. Immunol. 12, 117–139 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Tarlinton, D.M. Evolution in miniature: selection, survival and distribution of antigen reactive cells in the germinal centre. Immunol. Cell Biol. 86, 133–138 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Gershon, R.K. & Kondo, K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18, 723–737 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bretscher, P. & Cohn, M. A theory of self-nonself discrimination. Science 169, 1042–1049 (1970).

    Article  CAS  PubMed  Google Scholar 

  5. Noelle, R.J. & Snow, E.C. Cognate interactions between helper T cells and B cells. Immunol. Today 11, 361–368 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Cyster, J.G. B cell follicles and antigen encounters of the third kind. Nat. Immunol. 11, 989–996 (2010).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Vinuesa, C.G., Tangye, S.G., Moser, B. & Mackay, C.R. Follicular B helper T cells in antibody responses and autoimmunity. Nat. Rev. Immunol. 5, 853–865 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Cannons, J.L. et al. Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 32, 253–265 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Smith, K.G., Hewitson, T.D., Nossal, G.J. & Tarlinton, D.M. The phenotype and fate of the antibody-forming cells of the splenic foci. Eur. J. Immunol. 26, 444–448 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. MacLennan, I.C. et al. Extrafollicular antibody responses. Immunol. Rev. 194, 8–18 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Vinuesa, C.G. & Cyster, J.G. How T cells earn the follicular rite of passage. Immunity 35, 671–680 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Victora, G.D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592–605 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu, Y.J. et al. Mechanism of antigen-driven selection in germinal centres. Nature 342, 929–931 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Good-Jacobson, K.L. et al. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat. Immunol. 11, 535–542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bryant, V.L. et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J. Immunol. 179, 8180–8190 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Linterman, M.A. et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J. Exp. Med. 207, 353–363 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Winter, O. et al. Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood 116, 1867–1875 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Mosier, D.E., Mond, J.J. & Goldings, E.A. The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect. J. Immunol. 119, 1874–1878 (1977).

    CAS  PubMed  Google Scholar 

  20. Mond, J.J., Lees, A. & Snapper, C.M. T cell-independent antigens type 2. Annu. Rev. Immunol. 13, 655–692 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Bekeredjian-Ding, I. & Jego, G. Toll-like receptors–sentries in the B-cell response. Immunology 128, 311–323 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Peng, S.L. Signaling in B cells via Toll-like receptors. Curr. Opin. Immunol. 17, 230–236 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Alugupalli, K.R., Akira, S., Lien, E. & Leong, J.M. MyD88- and Bruton's tyrosine kinase-mediated signals are essential for T cell-independent pathogen-specific IgM responses. J. Immunol. 178, 3740–3749 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Eckl-Dorna, J. & Batista, F.D. BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation. Blood 113, 3969–3977 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Minguet, S. et al. Enhanced B-cell activation mediated by TLR4 and BCR crosstalk. Eur. J. Immunol. 38, 2475–2487 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Lanzavecchia, A. & Sallusto, F. Toll-like receptors and innate immunity in B-cell activation and antibody responses. Curr. Opin. Immunol. 19, 268–274 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Martin, F., Oliver, A.M. & Kearney, J.F. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617–629 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Braley-Mullen, H. Antigen requirements for induction of B-memory cells: studies with dinitrophenyl coupled to T-dependent and T-independent carriers. J. Exp. Med. 147, 1824–1831 (1978).

    Article  CAS  PubMed  Google Scholar 

  29. Garcia de Vinuesa, C., O'Leary, P., Sze, D.M., Toellner, K.M. & MacLennan, I.C. T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci. Eur. J. Immunol. 29, 1314–1323 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Garcia de Vinuesa, C. et al. Germinal centers without T cells. J. Exp. Med. 191, 485–494 (2000).

    Article  Google Scholar 

  31. Lentz, V.M. & Manser, T. Cutting edge: germinal centers can be induced in the absence of T cells. J. Immunol. 167, 15–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Weller, S. et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 104, 3647–3654 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Genestier, L. et al. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J. Immunol. 178, 7779–7786 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Cariappa, A. et al. Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes. Immunity 23, 397–407 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Martin, F. & Kearney, J.F. Marginal-zone B cells. Nat. Rev. Immunol. 2, 323–335 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Liu, Y.J., Oldfield, S. & MacLennan, I.C. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones. Eur. J. Immunol. 18, 355–362 (1988).

    Article  CAS  PubMed  Google Scholar 

  38. Zandvoort, A. & Timens, W. The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens. Clin. Exp. Immunol. 130, 4–11 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guinamard, R., Okigaki, M., Schlessinger, J. & Ravetch, J.V. Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response. Nat. Immunol. 1, 31–36 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Song, H. & Cerny, J. Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen. J. Exp. Med. 198, 1923–1935 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Phan, T.G., Gardam, S., Basten, A. & Brink, R. Altered migration, recruitment, and somatic hypermutation in the early response of marginal zone B cells to T cell-dependent antigen. J. Immunol. 174, 4567–4578 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Cinamon, G., Zachariah, M.A., Lam, O.M., Foss, F.W. Jr. & Cyster, J.G. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat. Immunol. 9, 54–62 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Zietara, N., Lyszkiewicz, M., Krueger, A. & Weiss, S. ICOS-dependent stimulation of NKT cells by marginal zone B cells. Eur. J. Immunol. 41, 3125–3134 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Hayakawa, K., Hardy, R.R. & Herzenberg, L.A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J. Exp. Med. 161, 1554–1568 (1985).

    Article  CAS  PubMed  Google Scholar 

  45. Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. Identification of a B-1 B cell-specified progenitor. Nat. Immunol. 7, 293–301 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Alugupalli, K.R. et al. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity 21, 379–390 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Defrance, T., Taillardet, M. & Genestier, L. T cell-independent B cell memory. Curr. Opin. Immunol. 23, 330–336 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. Baumgarth, N., Tung, J.W. & Herzenberg, L.A. Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin. Immunopathol. 26, 347–362 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Fagarasan, S. & Honjo, T. Intestinal IgA synthesis: regulation of front-line body defences. Nat. Rev. Immunol. 3, 63–72 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Macpherson, A.J. et al. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288, 2222–2226 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Hardy, R.R. B-1 B cells: development, selection, natural autoantibody and leukemia. Curr. Opin. Immunol. 18, 547–555 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Barral, P. et al. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc. Natl. Acad. Sci. USA 105, 8345–8350 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Chang, P.P. et al. Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat. Immunol. 13, 35–43 (2012).

    Article  CAS  Google Scholar 

  54. Detre, C. et al. SAP expression in invariant NKT cells is required for cognate help to support B-cell responses. Blood 120, 122–129 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Leadbetter, E.A. et al. NK T cells provide lipid antigen-specific cognate help for B cells. Proc. Natl. Acad. Sci. USA 105, 8339–8344 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bendelac, A., Savage, P.B. & Teyton, L. The biology of NKT cells. Annu. Rev. Immunol. 25, 297–336 (2007).

    Article  CAS  PubMed  Google Scholar 

  57. Venkataswamy, M.M. & Porcelli, S.A. Lipid and glycolipid antigens of CD1d-restricted natural killer T cells. Semin. Immunol. 22, 68–78 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Godfrey, D.I. & Berzins, S.P. Control points in NKT-cell development. Nat. Rev. Immunol. 7, 505–518 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Kitamura, H. et al. The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J. Exp. Med. 189, 1121–1128 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. King, I.L. et al. Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat. Immunol. 13, 44–50 (2012).

    Article  CAS  Google Scholar 

  61. Tonti, E. et al. Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4+ T cell help. J. Immunol. 188, 3217–3222 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Fujii, S., Shimizu, K., Hemmi, H. & Steinman, R.M. Innate Vα14+ natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol. Rev. 220, 183–198 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Puga, I. et al. B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat. Immunol. 13, 170–180 (2012).

    Article  CAS  Google Scholar 

  64. Litinskiy, M.B. et al. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3, 822–829 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mackay, F. & Schneider, P. Cracking the BAFF code. Nat. Rev. Immunol. 9, 491–502 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Mosier, D.E. & Subbarao, B. Thymus-independent antigens: complexity of B-lymphocyte activation revealed. Immunol. Today 3, 217–222 (1982).

    Article  CAS  PubMed  Google Scholar 

  67. Garcia De Vinuesa, C. et al. Dendritic cells associated with plasmablast survival. Eur. J. Immunol. 29, 3712–3721 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Balazs, M., Martin, F., Zhou, T. & Kearney, J. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity 17, 341–352 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Randolph, G.J., Jakubzick, C. & Qu, C. Antigen presentation by monocytes and monocyte-derived cells. Curr. Opin. Immunol. 20, 52–60 (2008).

    Article  CAS  PubMed  Google Scholar 

  70. Leon, B. & Ardavin, C. Monocyte-derived dendritic cells in innate and adaptive immunity. Immunol. Cell Biol. 86, 320–324 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Tezuka, H. et al. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 448, 929–933 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Craxton, A., Magaletti, D., Ryan, E.J. & Clark, E.A. Macrophage- and dendritic cell–dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Blood 101, 4464–4471 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Merluzzi, S. et al. Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells. Blood 115, 2810–2817 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Gauchat, J.F. et al. Induction of human IgE synthesis in B cells by mast cells and basophils. Nature 365, 340–343 (1993).

    Article  CAS  PubMed  Google Scholar 

  75. Erazo, A. et al. Unique maturation program of the IgE response in vivo. Immunity 26, 191–203 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Shinkai, K., Mohrs, M. & Locksley, R.M. Helper T cells regulate type-2 innate immunity in vivo. Nature 420, 825–829 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Wang, H.B. & Weller, P.F. Pivotal advance: eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production. J. Leukoc. Biol. 83, 817–821 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. Henz, B.M., Maurer, M., Lippert, U., Worm, M. & Babina, M. Mast cells as initiators of immunity and host defense. Exp. Dermatol. 10, 1–10 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Sokol, C.L. et al. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat. Immunol. 10, 713–720 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Spencer, L.A. & Weller, P.F. Eosinophils and Th2 immunity: contemporary insights. Immunol. Cell Biol. 88, 250–256 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Tacke, F. et al. Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery. J. Exp. Med. 203, 583–597 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chorny, A., Puga, I. & Cerutti, A. Innate signaling networks in mucosal IgA class switching. Adv. Immunol. 107, 31–69 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chu, V.T. et al. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat. Immunol. 12, 151–159 (2011).

    Article  CAS  PubMed  Google Scholar 

  84. Mack, M. et al. Identification of antigen-capturing cells as basophils. J. Immunol. 174, 735–741 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Kim, S., Shen, T. & Min, B. Basophils can directly present or cross-present antigen to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes. J. Immunol. 183, 3033–3039 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Denzel, A. et al. Basophils enhance immunological memory responses. Nat. Immunol. 9, 733–742 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Ruprecht, C.R. & Lanzavecchia, A. Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur. J. Immunol. 36, 810–816 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Gavin, A.L. et al. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science 314, 1936–1938 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Pasare, C. & Medzhitov, R. Control of B-cell responses by Toll-like receptors. Nature 438, 364–368 (2005).

    Article  CAS  PubMed  Google Scholar 

  90. Day, N. et al. Interleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses. J. Pediatr. 144, 524–526 (2004).

    Article  PubMed  Google Scholar 

  91. Ku, C.L. et al. IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease. J. Med. Genet. 44, 16–23 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Sweet, R.A. et al. Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo. Proc. Natl. Acad. Sci. USA 108, 7932–7937 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Snapper, C.M. et al. Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae. Trends Immunol. 22, 308–311 (2001).

    Article  CAS  PubMed  Google Scholar 

  94. Khan, A.Q., Chen, Q., Wu, Z.Q., Paton, J.C. & Snapper, C.M. Both innate immunity and type 1 humoral immunity to Streptococcus pneumoniae are mediated by MyD88 but differ in their relative levels of dependence on toll-like receptor 2. Infect. Immun. 73, 298–307 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chu, V.T. & Berek, C. Immunization induces activation of bone marrow eosinophils required for plasma cell survival. Eur. J. Immunol. 42, 130–137 (2012).

    Article  CAS  PubMed  Google Scholar 

  96. Wollenberg, I. et al. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J. Immunol. 187, 4553–4560 (2011).

    Article  CAS  PubMed  Google Scholar 

  97. Linterman, M.A. et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 17, 975–982 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chan, T.D. et al. Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J. Immunol. 183, 3139–3149 (2009).

    Article  CAS  PubMed  Google Scholar 

  99. Inamine, A. et al. Two waves of memory B-cell generation in the primary immune response. Int. Immunol. 17, 581–589 (2005).

    Article  CAS  PubMed  Google Scholar 

  100. Toyama, H. et al. Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 17, 329–339 (2002).

    Article  CAS  PubMed  Google Scholar 

  101. Hsu, M.C., Toellner, K.M., Vinuesa, C.G. & Maclennan, I.C. B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses. Proc. Natl. Acad. Sci. USA 103, 5905–5910 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Obukhanych, T.V. & Nussenzweig, M.C. T-independent type II immune responses generate memory B cells. J. Exp. Med. 203, 305–310 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Nie, Y. et al. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J. Exp. Med. 200, 1145–1156 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Taillardet, M. et al. The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells. Blood 114, 4432–4440 (2009).

    Article  CAS  PubMed  Google Scholar 

  105. Gaspal, F.M. et al. The generation of thymus-independent germinal centers depends on CD40 but not on CD154, the T cell-derived CD40-ligand. Eur. J. Immunol. 36, 1665–1673 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Toellner, K.M. et al. Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. J. Exp. Med. 195, 383–389 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University, Canberra, Australia

    Carola G Vinuesa & Pheh-Ping Chang

Authors
  1. Carola G Vinuesa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pheh-Ping Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carola G Vinuesa.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vinuesa, C., Chang, PP. Innate B cell helpers reveal novel types of antibody responses. Nat Immunol 14, 119–126 (2013). https://doi.org/10.1038/ni.2511

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.2511

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing