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B cell responses to a peptide epitope. II: Multiple levels of selection during maturation of primary responses
R Tuteja1, A Agarwal, L Vijayakrishnan
1Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
This report analyses murine primary humoral recognition of a linear domain (MEP 17-31) within a 100 amino acid polypeptide, MEP-1. An analysis of the early primary IgM response revealed that MEP 17-31 presented at least two distinct domains for pre-immune B cell recognition represented by MEP-1 residues 19-23 and 26-28. However, subsequent maturation into an IgG response saw an exclusive selection for the anti-MEP 19-23 component with loss of all alternate specificities. The IgM response to MEP 19-23 was oligoclonal and composed of diverse paratope phenotypes as evidenced by varied heavy chains of immunoglobulin V-D-J combinations and CDR3 sequences. In contrast to the oligoclonality of IgM mAb, the mature IgG response to MEP 19-23 appeared to derive predominantly from a single progenitor. It therefore appears that maturation of primary humoral responses to polypeptide antigens involves two distinct levels of selection. While there is selection for a restricted subset of the initially induced antibody fine-specificities, progression of the response also entails a reduction in clonal heterogeneity of B cells responding to the dominant epitope.
This report analyses murine primary humoral recognition of a linear domain (MEP 17-31) within a 100 amino acid polypeptide, MEP-1. An analysis of the early primary IgM response revealed that MEP 17-31 presented at least two distinct domains for pre-immune B cell recognition represented by MEP-1 residues 19-23 and 26-28. However, subsequent maturation into an IgG response saw an exclusive selection for the anti-MEP 19-23 component with loss of all alternate specificities. The IgM response to MEP 19-23 was oligoclonal and composed of diverse paratope phenotypes as evidenced by varied heavy chains of immunoglobulin V-D-J combinations and CDR3 sequences. In contrast to the oligoclonality of IgM mAb, the mature IgG response to MEP 19-23 appeared to derive predominantly from a single progenitor. It therefore appears that maturation of primary humoral responses to polypeptide antigens involves two distinct levels of selection. While there is selection for a restricted subset of the initially induced antibody fine-specificities, progression of the response also entails a reduction in clonal heterogeneity of B cells responding to the dominant epitope.