Restricted, canonical, stereotyped and convergent immunoglobulin responses

Abstract

One contribution of 13 to a theme issue 'The dynamics of antibody repertoires'. It is becoming evident that B-cell responses to particular epitopes or in particular contexts can be highly convergent at the molecular level. That is, depending on the epitope targeted, persons of diverse genetic backgrounds and immunological histories can use highly similar, stereotyped B-cell receptors (BCRs) for a particular response. In some cases, multiple people with immunity to a particular epitope or with a type of B-cell neoplasia will elicit antibodies encoded by essentially identical immunoglobulin gene rearrangements. In other cases, particular VH genes encode antibodies important for immunity against pathogens such as influenza and HIV. It appears that the conserved antibody structures driving these stereotyped responses are highly limited and selected. There are interesting and important convergences in the types of stereotyped BCRs induced in conditions of immunity and B-cell-related pathology such as cancer and autoimmunity. By characterizing and understanding stereotyped B-cell responses, novel approaches to B-cell immunity and in understanding the underlying causes of B-cell pathology may be discovered. In this paper, we will review stereotyped BCR responses in various contexts of B-cell immunity and pathology.

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

“…We observed signatures of convergent light-chain genes among public antibodies expressing the same CDR-H3 amino acid sequence (SI Appendix, Fig. S6B), contributing additional evidence to the hypothesis that public antibodies can be elicited in response to common immune stimuli (SI Appendix, Table S3) (40,(42)(43)(44)(45)54).…”

“…Public VH sequences have been reported to arise in individuals infected with certain pathogens and also at a low frequency in healthy donors (10,40,(42)(43)(44)54). However, the question of whether the light chains paired with public heavy chains are also shared among individuals had not been addressed.…”

Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity

“…Since both IGHV4-34 and IGKV3-20 are known to encode for antibodies that bind infectious antigens, it is possible that infection is the source of antigen selection that triggers CAD. 11 The highly homologous antibody gene sequences found in younger patients indicate that antigen selection in these patients may be different than that in other patients. Additionally, a lower mutation rate of IGKV3-20 was also correlated with younger age at diagnosis (P=0.012) ( Table 1).…”

Lupus anti-ribosomal P autoantibody proteomes express convergent biclonal signatures

“…A corollary of the serum autoantibody proteome analysis is that these lupus-specific autoantibodies are derived from a limited number of B-clonal precursors that have evaded early tolerance checkpoints and undergone antigen-driven clonal selection, expansion and affinity maturation in germinal centres. In a broader context, stereotyped B cell receptors are becoming recognized increasingly in infections, B cell cancers and autoimmune diseases, challenging the paradigm that immunoglobulin responses against the same antigen are determined randomly in different individuals [20]. It remains unclear as to why identical determinants are selected on autoantigens among different patients [13,21,22], and why their structural features appear to channel responses to a few shared clones.…”