CROSS-LINKING CD21 CD35 OR CD19 INCREASES BOTH B7-1 AND B7-2 EXPRESSION ON MURINE SPLENIC B-CELLS/

Activation of the complement cascade and ligation of complement C3 rec eptors on B cells represent an important bridge between innate and Ag- specific acquired immunity, We show here that cross-linking of mouse C D21 (complement receptor type 2, CR2, C3d receptor) and CD35 (compleme nt receptor type 1, CR1, C3b/C4b receptor) or co-cross-linking of CD21 /CD35 and surface IgM rapidly up-regulates both B7-1 and B7-2 expressi on on murine resting splenic B cells, CD21/CD35-mediated up-regulation of both B7-1 and B7-2 expression is observed within 14 h, while other stimuli up-regulate only B7-2 but not B7-1 at this early time point, Consistent with the increase in B7 revels, BALB/c B cells on which sur face IgM and CD21/CD35 have been co-cross-linked stimulate C57BL/6 T c ells more effectively than controls. This CD21/CD35-enhanced allogenei c MLR is blocked nearly completely by anti-B7-2 mAbs and partially by anti-B7-1 mAbs, In addition, cross-linking of CD19, which is physicall y associated with CD21/CD35, leads to increased B7-1 and B7-2 expressi on. These data suggest that CD21/CD35 ligation results in enhanced B c ell Ag presentation using costimulatory mechanisms shared with other a ctivators and thus works cooperatively in this process, Rapid up-regul ation of B7-1 expression, a unique response to CD21/CD35 and CD19 cros s-linking, may be a particularly important effect of C3-containing lig ands, We propose that CD21/CD35- and CD19-mediated B7-1 and B7-2 up-re gulation is an important mechanism by which complement activation link s innate and acquired immunity.