THE BALB C MOUSE B-CELL RESPONSE TO PIGEON CYTOCHROME-C INITIATES AS A HETEROCLITIC RESPONSE SPECIFIC FOR THE SELF ANTIGEN MOUSE CYTOCHROME-C/

Direct evidence is presented in support of the longstanding but unprov en hypothesis that B lymphocytes specific for self antigens (Ags) can be used in the immune response to foreign Ags. We show that the B cell s in BALB/c mice responding early to pigeon cytochrome c (CYT) produce antibodies that recognize and bind the major antigenic site on mouse CYT with greater affinity than they bind pigeon CYT-i.e., they are het eroclitic for the self Ag. Furthermore, these B cells express the same combination of immunoglobulin variable region (V) genes that are know n to be used in B-cell recognition of mouse CYT. Over time, the respon se to pigeon CYT becomes more specific for the foreign Ag through the recruitment of B cells expressing different combinations of V genes an d, possibly, somatic mutation of the mouse CYT-specific B cells from e arly in the response. Cross-recognition of pigeon CYT by mouse CYT-spe cific B cells results from the sharing of critical amino acid residues by the two Ags. Although B-cell recognition of the self Ag, mouse CYT , is very specific, which limits the extent to which foreign Ags can c ross-activate the autoreactive B cells, it is possible that polyreacti ve B cells to other self Ags may be used more frequently in response t o foreign Ags.