Abstract
The induction of a humoral response depends upon efficient cross-linking by antigen of surface immunoglobulin on primary B lymphocytes. We demonstrate here the presence of a glycosylphosphatidylinositol-linked isoform of membrane IgD (mIgD) receptors on murine resting B cells. This subset was constitutively localized to cell membrane raft microdomains. Its stimulation resulted in the activation of cAMP-dependent signaling pathways, which integrated with signals derived from the transmembrane mIgD receptors. This, in turn, provided a mechanism by which the activation status of the target cells could be variably regulated. Thus, by partitioning receptor activity, preimmune B cells can moderate the extent to which they are activated, depending upon the strength of the antigenic stimulus.
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Supported by a grant from the Indian Council of Medical Research (to K. V. S. R.).
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Web Fig. 1.
Activation of resting B lymphocytes with anti-IgD. Purified resting B cells were stimulated with a final concentration of 10 μg/ml of anti-IgD as described in the Methods. Following this, cells were analyzed for surface expression of the markers indicated by flow cytometry (a). Labeling with the appropriate isotype-matched control Ig yielded profiles that were superimposable with those for unstimulated cells. Results depicted are representative of eight independent experiments. (b) GCs obtained when anti-IgD-stimulated B cells were loaded with peptide CT3 and transferred into CT3-primed BALB/c IgHb mice (left panel). Specific GCs were identified as those containing IgHa-specific (IgG1a plus IgMa, red) and PNA+ (blue) cells. The right panel shows the empty follicles in CT3-primed BALB/c IgHb mice that had received peptide CT3-loaded unstimulated cells. (PDF 1065 kb)
Web Fig. 2.
Membrane distribution of sIgD receptors. Detergent-insoluble (fractions 4-6) and -soluble (fractions 10-12) fractions from cells lysed in Triton X-100 were resolved on a 10% polyacrylamide gel and then transferred onto a nitrocellulose membrane. These were then immunoblotted for GM1 ganglioside with biotinylated choleratoxin B subunit (CTB) or for IgD (sIgD) or CD45R (B220). The distribution of sIgD receptors in unstimulated cells and in cells stimulated with 10 μg/ml of anti-IgD (5 min at 37 °C) are shown in the panels identified as sIgD(u) and sIgD(s), respectively. The lowest panel, described as CTB(mcd), shows the effect of treatment of cells with MCD (10 mM) on GM1 gangliosides. (PDF 255 kb)
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Chaturvedi, A., Siddiqui, Z., Bayiroglu, F. et al. A GPI-linked isoform of the IgD receptor regulates resting B cell activation. Nat Immunol 3, 951–957 (2002). https://doi.org/10.1038/ni839
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DOI: https://doi.org/10.1038/ni839
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