ANTIGENS VARYING IN AFFINITY FOR THE B-CELL RECEPTOR INDUCE DIFFERENTIAL B-LYMPHOCYTE RESPONSES

The B cell receptor (BCR) triggers a variety of biological responses t hat differ depending upon the properties of the antigen. A panel of M1 3 phage-displayed peptide ligands with varying affinity for the 3-83 a ntibody was generated to explore the role of antigen-BCR affinity in c ell activation studies using primary 3-83 transgenic mouse B cells. Mu ltiple parameters of activation were measured. T cell-independent B ce ll proliferation, antibody secretion, induction of germline immunoglob ulin gamma 1 transcripts, and B cell production of interleukin (IL) 2 and interferon gamma responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the contex t of CD40 signaling were only weakly dependent on antigen affinity. Bi ochemical analysis revealed that at saturating ligand concentrations t he ability of phage to stimulate some early signaling responses, such as Ca++ mobilization and tyrosine phosphorylation of syk or Ig alpha, was highly affinity dependent, whereas the ability to stimulate Lyn ph osphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signa ling by antigen determines whether an antibody response will be T inde pendent or dependent is discussed.