Properties of mouse CD40: the role of homotypic adhesion in the activation of B cells via CD40

✍ Scribed by Gerry G. B. Klaus; Mary Holman; Jhagvaral Hasbold

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 693 KB
• Volume: 24
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830241121

✦ Synopsis

Stimulation of human Bcells via CD40 is known to induce their homotypic aggregation. We show here that anti-mouse CD40 monoclonal antibodies (mAb) also induce B cells to form large, spherical, extremely stable clusters. This clustering is markedly enhanced by co-stimulation with either interleukin-4 (IL-4) or anti-immunoglobulin (Ig). The aggregation is slow in onset, and is largely (but not completely) abrogated by anti-LFA-1 mAb, but not by mAb directed against other potentially important adhesion molecules on B cells. Anti-LFA-1 mAb also partially suppressed DNA synthesis induced by anti-CD40, but not by other B cell mitogens, suggesting that clustering is an important component of B cell activation via CD40.This concept is supported by analyses of the phenotype of clustered B cells: the cells within clusters express higher levels of various activation markers, and also more of them are in cell cycle than non-clustered cells. These results therefore suggest that CD40 stimulation may either induce B cells to secrete soluble factors which act in an autocrine way to promote B cell activation, or that clustering generates cell contact-mediated signals which are important in the activation cascade.