Immunoglobulin variable-region (V) genes, it is now recognized, do not encode specific receptors for T lymphocytes. Classical observations on T-cell expression of immunoglobulin idiotypes 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-mu antibodies from birth. 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 interactions in the selection of available lymphocyte repertoires before antigenic challenge. Previously described influences of B cells and/or antibodies on the T-helper (Th) cell compartment 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. 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.

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The progeny ofBALB/c female mice actively immunized with the trinitrophenyl-binding myeloma protein MOPC460 and producing anti-idiotypic antibodies during pregnancy were compared with mice born of normal mothers for several characteristics of B lymphocytes and their precursors. In all cases, maternal anti-idiotypic immunity resulted in the suppression of the expression of that idiotype by immunocompetent cells in the progeny, as shown by limiting-dilution analysis in single clones of mitogen-reactive IgM-secreting cells. At critical concentrations of circulating maternal antibodies, suppression of the antibody idiotype was found to be accompanied by a large increase in the total number of mature small B lymphocytes. This increase can be accounted for by the selective expansion of B cells bearing nonimmunoglobulin surface structures crossreactive with a MOPC460 idiotope recognized by a monoclonal antibody. In addition, the large majority ofnewly formed mature B lymphocytes, as well as a large fraction of immunoglobulin-negative cells in the bone marrow of suppressed mice, bear such nonimmunoglobulin MOPC460 crossreactive determinant(s). These results suggest that the suppression of a given "recurrent" idiotype has profound consequences for a large part of the immune system. Some antibody idiotypes in the mouse being "recurrent," the possibility exists of studying their suppression in normal animals. This has been achieved by treatment with anti-idiotypic antibodies (1, 2) and by the transfer of cells from animals previously suppressed with antibodies (3). The mechanisms involved in idiotypic suppression are thought to reflect physiological regulatory processes and may be useful in the control of undesirable reactivities. Suppression ofidiotype expression has also been observed in the progeny of females immunized with that idiotype (4).These (6).We have studied the suppression of a combining-site-related idiotope of the trinitrophenyl (TNP)-binding myeloma protein MOPC460 identified by a monoclonal antibody (7). Such an idiotype is recurrent in BALB/c mice, as it can be detected in a variable proportion of antibodies produced by every mouse of this strain (8) and is also expressed on nonimmunoglobulin membrane structures on cells of the B-cell lineage (6).We report here the possibility of inducing neonatal suppression ofthe MOPC460 idiotype in a completely syngeneic system by the anti-idiotypic immunity of mothers during pregnancy and the finding that such an idiotypic suppression is accompanied by profound alterations in the development of a large part of the B-cell system. MATERUILS AND METHODSMice. BALB/c mice 1 to >20 weeks old were obtained from the Pasteur Institute (Paris) or from the Institute for Biomedical Research (Fiullinsdorf, Switzerland). Normal or immunized BALB/c females were mated with normal BALB/c males and the progeny were studied over an 8-week period.Anti-Idiotypic Antibodies. A monoclonal anti-BALB/c idiotopic antibody, clone F6(51), described by Buttin et al. (7), was used for de...