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.