Establishment of idiotypic helper T-cell repertoires early in life

Abstract

Immunoglobulin variable-region (V) genes, it is now recognized, do not encode specific receptors for T lymphocytes^1–4. Classical observations on T-cell expression of immunoglobulin idiotypes^5,6 had remained unexplained until recent experiments showed that immunoglobulin idiotypes expressed by T lymphocytes in normal mice are absent in cells of the same specificity isolated from donors whose B-cell system has been suppressed by administration of anti-μ antibodies from birth^7,8. This observation provided evidence for the ‘learning’ of T-cell idiotypes from the B-cell/antibody system and, therefore, for the importance of idiotypic network interactions⁹ in the selection of available lymphocyte repertoires before antigenic challenge. Previously described influences of B cells and/or antibodies on the T-helper (T_h) cell compartment¹⁰ would appear to operate at the level of clonal repertoires by complementarities with defined immunoglobulin idiotypes. Other authors, however, had previously shown the striking stability of T-cell idiotype expression in chimaeric animals reconstituted with T and B cells originating from donors showing differential idiotype expression^11,12. We have now investigated this apparent discrepancy and present here results demonstrating that immunoglobulin-dependent selection of T-cell (idiotypic) repertoires only operates for the first 3 weeks of life.