Fig. 7.
Proposed models of cognate vs. non-cognate and polyclonal B cell activation. a Classical cognate activation by antigens. Arrayed antigens (green) on the surface of a pathogen or an antigen-presenting cell stimulate BCR signaling, expression of activation markers CD69, CD86/80 and CD54, internalization of the BCR-antigen complex, and antigen processing for presentation on MHC-II. A complementary T helper cell (Th) provides costimulatory signals through CD40L and cytokines such as IL-2, which initiate a B cell differentiation program into antibody-secreting plasma cells. b Proposed model for non-cognate and polyclonal activation. B cell superantigens like SpA crosslink conserved BCR sites, downmodulate BCR and CD19 expression, and pan-activate B cells irrespective of their antigen specificity. We propose multivalent lectins like BambL achieve a similar effect by crosslinking BCR glycans. In the absence of sufficient survival and differentiation signals, the B cells succumb to exhaustion in a form of activation-induced cell death