Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B cells

In the present study the capacity of early fetal B cells to produce Ig was investigated. It is shown that B cells from fetal liver, spleen, and bone marrow (BM) can be induced to produce IgM, IgG, IgG4, and IgE, but not IgA, in response to IL-4 in the presence of anti-CD40 mAb or cloned CD4+ T cells. Even splenic B cells from a human fetus of only 12 wk of gestation produced these Ig isotypes. IFN-CY, IFN-7, and transforming growth factor-/I inhibited IL-4411- duced IgE production in fetal B cells, as described for mature B cells. The majority of B cells in fetal spleen expressed CD5 and CDlO and ~ 9 9 %of B cells in fetal BM were CD10+. Highly purified CDlO+,CD19+i mmature B cells and CD5+,CD19+B cells could be induced to produce Ig, including IgG4 and IgE, in similar amounts as unseparated CD19+ B cells. Virtually all CD19+ cells still expressed CDlO after 12 days of culture. However, the IgEproducing cells at then d of the culture period were found in the CD19-,CDlO- cell population, suggesting differentiation of CD19+,CD10+ B cells into CD19-,CD10- plasma cells. Pre-B cells are characterized by their lack of expression of surface IgM (sIgM). Only 30 to 40% of BM B cells expressed sIgM. However, in contrast to sIgM+,CDlO+,CD19+ immature B cells, sorted sIgM-,CDlO+,CDlS+ pre-B cells failed to differentiate into Ig-secreting cells under the present culture conditions. Addition of IL-6 to these cultures was ineffective. Taken together, these results indicate that fetal CD5+ and CDlO+ B cells are mature in their capacity to be induced to Ig isotype switching in vitro as soon as they express sIgM.