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.