Suppression of a "recurrent" idiotype results in profound alterations of the whole B-cell compartment.

Abstract

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...

Maternal transmission of idiotypic network interactions selecting available T cell repertoires

“…We observe here, therefore, a nongenetic transmission to progenies of a phenotype not expressed by the female parent. Such maternally derived suppression has been previously described for expression of Id in antibody responses and shown to result in wide alterations in the B cell compartment [15]. The present experiments are the first, to our knowledge, addressing this question at the T cell level and consolidate the fundamental importance of maternal influences in the ontogeny of immune systems and selection of available repertoires.…”

Turning (Ir gene) low responders into high responders by antibody manipulation of the developing immune system.

“…In this context, the determinant influences of the maternal immune system in establishing repertoires of progenies acquire particular relevance. We had previously described this type of influence upon the B-cell compartment of newborns (38), and they are extended here to the T-cell compartment and to later stages in life. By inference, we can expect this fundamental "learning" process to occur with every immune system from the immunological status of the mother at the time of pregnancy, which, in turn, depends on its own ontogeny.…”

Normal serum immunoglobulins participate in the selection of peripheral B-cell repertoires.

“…Serum immunoglobulins from normal BALB/c donors could merely serve as carriers of exogenous antigens or directly modify the dynamics of B-cell selection. These changes may be due to the elimination of cells expressing VH7183 gene products by specific idiotype-like interactions (16), which have been documented to induce idiotype suppression in newborn mice (35,36). Expression of the VH7183 family correlates well with antibody multireactivity of recently formed B cells (37), which can be more readily silenced than mature B cells (38), and deletion of VH7183-bearing cells was shown to occur at the pre-B-cell level in the bone marrow of adult SPF BALB/c mice (11).…”