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-α, IFN-γ, and transforming growth factor-β inhibited IL-4-induced IgE production in fetal B cells, as described for mature B cells. The majority of B cells in fetal spleen expressed CDS and CD10 and >99% of B cells in fetal BM were CD10⁺. Highly purified CD10⁺,CD19⁺ immature 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 CD10 after 12 days of culture. However, the IgE-producing cells at the end of the culture period were found in the CD19^-,CD10^- 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⁺,CD10⁺,CD19⁺ immature B cells, sorted sIgM^-,CD10⁺,CD19⁺ 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 CD10⁺ B cells are mature in their capacity to be induced to Ig isotype switching in vitro as soon as they express sIgM.