Activated B cells express increased levels of costimulatory molecules in young autoimmune NZB and (NZB x NZW)F-1 mice

Polyclonal B cell activation is a hallmark of autoimmune disease in NZB and (NZB x NZW)F-1 (NZB/W) mice. However, the mechanism by which this activate d cell subset facilitates disease development is unknown. We recently showe d that resting B cells from these mice demonstrate enhanced expression of c ostimulatory molecules in response to CD40 crosslinking (Jongstra-Bilen et at, J. Immunol. 159,5810-5820, 1997). This led us to question whether activ ated B cells expressed costimulatory molecules in vivo. Using flow cytometr y we found that NZB and NZB/W mice have an increased proportion of splenic B cells expressing B7.1 and elevated levels of B7.2 and ICAM-1. These B cel ls isolate within the low-density activated population and possess the phen otypic characteristics of marginal zone B cells. The levels of B7.1 on the activated B cell population are similar to those induced by CD40 stimulatio n raising the possibility that activated B cells in NZB and NZB/W mice prov ide costimulatory signals to self-reactive T cells leading to loss of toler ance. (C) 2000 Academic Press.