DIFFERENTIAL ACTIVATION REQUIREMENTS OF ISOTYPES, SWITCHED B-CELLS

In the present studies, we compared the activation requirements of sIg M(+)/sIgD(+) B cells with those of isotype-switched sIgM(-)/sIgA(+) B cells. We found that whereas sIgM(+) B cells respond to T cell-indepen dent (TI) and T cell-dependent (TD) Ag with no significant bias toward one stimulus, sIgA(+) B cells were deficient in their ability to resp ond to antigen receptor cross-linking but responded remarkably well to TD stimuli. Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dext ran), arti-kappa-dextran, or various immobilized anti-IgA antibodies ( Ab) induced only low-level IgA B cell proliferation and no IgA secreti on in the presence of various lymphokines; in marked contrast, sIgA(+) B cells responded to cognate and noncognate T cell stimulation as wel l as to stimulation by CD40 ligand-bearing fibroblasts by secreting la rge amounts of IgA (up to 240000 ng/ml per 10(5) cells). This pattern of sIgA(+) B cell responsiveness was noted with both germinal center p eanut agglutinin(hi) (PNA(hi)) and non-germinal center PNA(lo) B cells . In confirmation of these results, whole Peyer's patch or lamina prop ria cell populations containing less than 15% sIgA(+) B cells stimulat ed with a noncognate T cell stimulus or T cell membranes secreted main ly IgA (68%-94% of the total Ig secreted) and relatively little IgM. T he strict T cell dependence of IgA B cell activation and differentiati on provides important insights into immune responses of mucosal tissue s and must be considered in the development of vaccines, particularly those designed to stimulate mucosal tissues containing large numbers o f isotype-switched B cells.