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

Abstract The 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 of Staphylococcus 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, whereas high levels of IgG were secreted by CD5 − B cells.