Proliferation and differentiation of human CD5+and CD5−B cell subsets activated through their antigen receptors or CD40 antigens

摘要

AbstractThe pan‐T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30 of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+and CD5−B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+B cells were positively selected by panning or by sorting from tonsils. Two‐color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+B cells displayed most of the phenotypic features of mantle zone B cells. CD5+B cells could be stimulated for DNA synthesis by mitogenic concentrations ofStaphylococcus aureus, Cowan I strain (SAC), insolubilized anti‐IgM antibodies, immobilized anti‐CD40 antibodies and phorbol 12‐myristate 13‐acetate (PMA). The growth‐response of small dense CD5−B cells to these T cell‐independent mitogens was comparable to that of CD5+B cells, whereas the low‐density,in vivo‐activated, CD5−B cells were only marginally stimulated by Ig‐cross‐linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)‐2 and IL‐4. When used in co‐stimulation with immobilized anti‐CD40 antibodies, IL‐4 promoted growth of CD5+and CD5−B cells, whereas IL‐2 displayed only moderate stimulatory effects. CD5+and CD5−B cells differentiated into Ig‐secreting cells when they were co‐cultured with SAC or cross‐linked anti‐CD40 antibodies and IL‐2. However, IgM constituted the major component of the Ig response of CD5+B cells,