Enhanced IgA Class Switching in Marginal Zone and B1 B Cells Relative to Follicular/B2 B Cells

Abstract

Mouse splenic marginal zone (MZ) B cells and B1 B cells enriched in the peritoneal cavity respond preferentially to T cell-independent Ags compared with follicular (FO)/B2 B cells. Despite the differential responses of B cell subsets to various stimuli, and despite the need for multiple stimuli to induce IgA class switching, the relative contribution of B cell subpopulations to IgA production is unknown. By culturing purified B cell populations, we find that MZ and peritoneal B1 cells switch more readily to IgA than do splenic FO or peritoneal B2 cells in BLyS/LPS/TGF-β. Addition of IL-4, IL-5, and anti-IgD dextran to the cultures enhances IgA switching in FO/B2 and MZ B cells to a similar frequency, but this treatment suppresses IgA class switching in B1 cells. Thus, IgA switching differs among purified B cell subsets, suggesting that individual B cell populations could contribute differentially to IgA expression in vivo, depending on available stimuli.

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

“…97 In addition, B1 cells have been reported to switch to IgA more promptly than B2 cells in response to antigen. 98 Given our data, we hypothesize that the early IgA induced against QARVLAVERY may be a result of direct or indirect stimulation of B1 cells and that the additional priming of B1 cells may be responsible for the unusually high IgA observed against QARVLAVERY.…”

The regulation of IgA class switching

“…This circumstance possibly reflects the unique antigen recognition profile of B-1 and marginal-zone B cells, which express both germline gene-encoded (that is, TLRs) and somatically recombined (that is, BCRs) antigen receptors 103 . When exposed to BAFF, LPS and TGFβ1, B-1 and marginal-zone B cells switch to IgA expression more readily than B-2 cells 78 . Such distinctive responsiveness may reflect the stimuli available in the microenvironments in which these B-cell subsets usually operate.…”

“…These antibodies mediate immune exclusion of commensals and provide limited protection against some pathogens, including rotaviruses and Salmonella typhimurium [75][76][77] . Systemic T-cell-independent IgA responses also exist and these appear to require B cells in the marginal zone of the spleen 1,78 . Similar to B-1 cells, mouse marginal-zone B cells express polyreactive IgA (and IgM) antibodies that may provide a second line of defence against commensal bacteria that breach the epithelial-cell barrier 1,71 .…”

“…Although sufficient to initiate IgA CSR 41 , TGFβ1 and LPS require additional signals, such as BCR engagement by dextran-conjugated IgD-specific antibodies, to induce significant IgA expression and secretion 58,78 . These additional signals may be needed to optimize the expansion and differentiation of the B cells that have undergone IgA CSR in response to TGFβ1 and LPS.…”

“…Surprisingly, NF-κB is not required for the activation of I α promoters, which is highly dependent on other transcription factors [45][46][47][48]55,97 . Instead, NF-κB may be required by TLRs to induce the expression of AID 26,34,98,99 .Although sufficient to initiate IgA CSR 41 , TGFβ1 and LPS require additional signals, such as BCR engagement by dextran-conjugated IgD-specific antibodies, to induce significant IgA expression and secretion 58,78 . These additional signals may be needed to optimize the expansion and differentiation of the B cells that have undergone IgA CSR in response to TGFβ1 and LPS.…”