B-CELL RESPONSES TO A PEPTIDE EPITOPE .2. MULTIPLE LEVELS OF SELECTION DURING MATURATION OF PRIMARY RESPONSES

This report analyses murine primary humoral recognition of a linear do main (MEP 17-31) within a 100 amino acid polypeptide, MEP-1. An analys is of the early primary IgM response revealed that MEP 17-31 presented at least two distinct domains for pre-immune B cell recognition repre sented by MEP-1 residues 19-23 and 26-28. However, subsequent maturati on into an IgG response saw an exclusive selection for the anti-MEP 19 -23 component with loss of all alternate specificities. The ISM respon se to MEP 19-23 was oligoclonal and composed of diverse paratope pheno types as evidenced by varied heavy chains of immunoglobulin V-D-J comb inations and CDR3 sequences. In contrast to the oligoclonality of IgM mAb, the mature IgG response to MEP 19-23 appeared to derive predomina ntly from a single progenitor. It therefore appears that maturation of primary humoral responses to polypeptide antigens involves two distin ct levels of selection. While there is selection for a restricted subs et of the initially induced antibody fine-specificities, progression o f the response also entails a reduction in clonal heterogeneity of B c ells responding to the dominant epitope.