Chronic in vivo depletion of CD4 T cells begun in utero inhibits gut B cell differentiation.

We studied the role of CD4 T cells on the ontogeny of mucosal IgA compartment. We treated C57 BL/6 mice, beginning in utero and for 4 weeks thereafter, with anti-CD4 monoclonal antibody. Mice were evaluated at 1, 3, and 5 weeks after stopping the treatment. At 1 week, anti-CD4-treated mice had no detectable CD4 T cells in spleen or Peyer's patches. These CD4-depleted mice demonstrated a 40% reduction of surface Peyer's patch IgA+ B cells and a marked decrease in jejunal IgA secretion. By 5 weeks, CD4 T cells were detectable in spleen and Peyer's patch and the number of surface IgA+ B cells in Peyer's patch was increased, but they remained less than the control levels. Jejunal IgA secretion recovered to the control level by 5 weeks. LPS induced normal levels of in vitro IgM secretion by Peyer's patch B cells in anti-CD4-treated mice; thus, treatment with anti-CD4 does not nonspecifically inhibit the gut B cell compartment. This study demonstrates that CD4 T cell depletion begun in utero significantly inhibits the differentiation of mucosal B cells to IgA-secreting cells and partially inhibits switching to IgA+ B cells in Peyer's patch.