B cell responses to a peptide epitope. II: Multiple levels of selection during maturation of primary responses.
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.
Tuteja
R
R
Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Agarwal
A
A
Vijayakrishnan
L
L
Nayak
B P
BP
Gupta
S K
SK
Kumar
V
V
Rao
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016056:Immunodominant Epitopes / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D017931:DNA Primers; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C073096:multiple-epitope polypeptide 1, Hepatitis B virus; D004247:DNA