Characterization of a novel CD2+ human thymic B cell subset.

Abstract

In the present study, it is demonstrated that functionally mature B cells are present in human thymus early during fetal life. Interestingly, 46 +/- 7% of fetal and postnatal thymic CD19+ B cells co-expressed CD2. Adult peripheral blood or splenic B cells were CD2-, and < 5% of fetal BM or fetal splenic CD19+ cells expressed CD2, indicating that CD2 is expressed preferentially on thymic B cells. Fetal thymic CD2+ B cells have a mature phenotype, because they are CD20+, CD40+, and surface IgM+, but they lack CD34 expression. They are also functionally mature because total thymic cell populations or highly purified CD2+ thymic B cells underwent Ig isotype switching and differentiation into Ig-secreting cells in a similar fashion as conventional B cells after culturing in the presence of IL-4 and activated cloned CD4+ T cells and anti-CD40 mAb cross-linked to Fc gamma RII/CDw32 transfected into murine L cells (Fc gamma RII+/L). Engagement of CD2 on thymic B cells by LFA-3+ L cell transfectants, anti-CD2 mAb cross-linked to Fc gamma RII+/L, or a mitogenic combination of anti-CD2 mAb did not result in proliferation or Ig production under the present conditions. However, anti-CD2 mAb enhanced IL-4 dependent Ig-synthesis by thymic B cells in the presence of activated CD4+ T cells, but they were ineffective when the B cells were activated by anti-CD40 mAb, suggesting that the anti-CD2 mAb stimulated antibody production indirectly via CD4+ T cells. Similarly, IL-7 enhanced IL-4-induced Ig production in the presence of CD4+ T cells. This effect of IL-7 also appeared to be indirect because no enhancement in Ig levels was observed in cultures of purified thymic B cells. Collectively, our results indicate that functionally mature B cells are present in human thymus early during fetal life, and that thymic CD2+, CD19+, sIgM+ cells represent a subset of bona fide B cells, which can be induced to Ig isotype switching and Ig production in vitro in a similar fashion as conventional B cells.