Quiescent memory B cells in human peripheral blood co-express bcl-2 and bcl-x(L) anti-apoptotic proteins at high levels

Abstract

The anti-apoptotic proteins bcl-2 and bcl-xL seem to exhibit strictly opposite expression patterns in normal lymphoid cell differentiation stages, with bcl-2 low and bxl-xL high in immature and mature proliferating cells, the reverse being the case in recirculating quiescent cells. However, it is in fact not known whether recirculating memory cells are bcl-xL low or high. We analyzed memory (immunoglobulin isotype-switched) B cells in human peripheral blood, which were small lymphocytes in the G0 phase of the cell cycle, but proliferated better than naive B cells in response to Staphylococcus aureus Cowan I. Ex vivo these cells co-expressed bcl-2 together with bcl-xL mRNA and protein at high levels. The mcl-1 mRNA level was low. The bcl-xL mRNA level decreased during culture in medium containing fetal calf serum, which implies that it is maintained in vivo by continuous or frequent, non-mitogenic signal(s). The high bcl-xL expression of memory B cells may be relevant with regard to their longevity and/or their capacity to undergo an accelerated secondary type immune response.