Differential activation requirements of isotype‐switched B cells

Abstract

In the present studies, we compared the activation requirements of sIgM+/sIgD+ B cells with those of isotype-switched sIgM-/sIgA+ B cells. We found that whereas sIgM+ B cells respond to T cell-independent (TI) and T cell-dependent (TD) Ag with no significant bias toward one stimulus, sIgA+ B cells were deficient in their ability to respond to antigen receptor cross-linking but responded remarkably well to TD stimuli. Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dextran), anti-kappa-dextran, or various immobilized anti-IgA antibodies (Ab) induced only low-level IgA B cell proliferation and no IgA secretion in the presence of various lymphokines; in marked contrast, sIgA+ B cells responded to cognate and noncognate T cell stimulation as well as to stimulation by CD40 ligand-bearing fibroblasts by secreting large amounts of IgA (up to 240 000 ng/ml per 10(5) cells). This pattern of sIgA+ B cell responsiveness was noted with both germinal center peanut agglutininhi (PNAhi) and non-germinal center PNAlo B cells. In confirmation of these results, whole Peyer's patch or lamina propria cell populations containing less than 15% sIgA+ B cells stimulated with a noncognate T cell stimulus or T cell membranes secreted mainly IgA (68%-94% of the total Ig secreted) and relatively little IgM. The strict T cell dependence of IgA B cell activation and differentiation provides important insights into immune responses of mucosal tissues and must be considered in the development of vaccines, particularly those designed to stimulate mucosal tissues containing large numbers of isotype-switched B cells.

B Cell Memory in xid Mice is Long‐Lived Despite Reduced Memory B Cell Frequency

“…If expansion and differentiation of memory B cells were to depend more on stimulation by CD40L than on pathways using Btk, such as B-cell receptor stimulation [25], then the kinetics and magnitude of the secondary response in xid mice may well be similar to that in wild type. Consistent with this proposal is the observation that memory B cells from Peyer's patches respond to a greater extent, as measured by antibody secretion and proliferation, to stimulation through CD40 than to crosslinking of the B cell receptor [26].…”

Discordance between IgA Switching at the DNA Level and IgA Expression at the mRNA Level in IgA-Deficient Patients

“…Decreased membrane C␣ mRNA may also have a negative effect on the differentiation of these B cells, since differentiation of IgA-switched B cells requires T cell help (21). B cells use their B cell receptor to capture small amounts of their specific antigens so that they can present specific antigen-derived peptides to T cells for help.…”

CD19-deficient mice exhibit poor responsiveness to oral immunization despite evidence of unaltered total IgA levels, germinal centers and IgA-isotype switching in Peyer's patches

“…Especially, a defect in the CD40-CD40L interaction would explain the lack of B cell differentiation to these isotypes, [23]. To address this possibility we isolated B cells from PP or spleen and cultured these cells with different doses of anti-CD40 antibody or fibroblasts expressing CD40L together with cytokines previously shown to promote proliferation and IgA production by intestinal B cells [14,24]. We found that the response to anti-CD40 antibody or CD40L was dramatically reduced in CD19-deficient B cells (Fig.…”