Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host.

Abstract

Suppressor T-cell factor(s) (TsFj) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF, is restricted by genes linked to Igh-) allotypic markers. TsFj obtained from B6Jgh-1" mice was unable to suppress the immune response in B6.Jgh-1b mice and vice versa. However, TsFj prepared from B6.Igh-1 T cells "parked" in an Igh-congeneic B6.Igh-lb environment displays an additional restriction specificity of the host. Thus, TsF, prepared from these Igh-chimeric mice suppressed immune responses in both B6.Jgh-1" (donor) and B6Jgh-lb (recipient) mice but not in mice of the unrelated strain BALB/ c.Igh-la. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response.The expression of idiotypic determinants, controlled by genes linked to the Igh locus, on T cells was initially reported by Binz and Wigzell (1). Since then, many laboratories including our own have provided evidence for the expression of immunoglobulin idiotypic determinants on various T-cell subpopulations (2-6). In addition, Igh-controlled specificities have been reported to function as restriction elements in various cellular-interaction pathways (7,8). Moreover, the role of Igh genes and their products in the development of the T-cell repertoire has also been suggested by the observation that Igh-linked genes control the crossreactive patterns of alloreactive cytotoxic T cells (CTLs) (9). These findings were generally interpreted to indicate that T and B cells may use identical Ig heavy chain variable-region (VH) genes to encode their antigen-specific receptors.More recently, the establishment of functional T-cell clones or hybrids and the construction of the appropriate nucleic acid probes from B cells have stimulated analysis of the VH genes in T cells bearing the corresponding Ig idiotypes. The results uniformly failed to reveal any evidence of rearrangement of Ig heavy chain genes in T-cell clones or hybrids expressing Ig idiotypic specificity (10, 11).An alternative explanation for expression of Ig idiotypes on T cells and their factors is that their presence and the Ighlinked functional restrictions they determine are indeed not the result of the expression of VH genes in T cells but rather reflect the influence of Ig idiotypes on B cells during T-cell differentiation and/or in the course of T-cell-specific responses.Thus, we postulate that clonal expansion of a B-cell subpopulation bearing a particular idiotypic specificity may stimulate the clonal expansion of corresponding anti-idiotypic T or B cells. These anti-idiotypic T cells may, in turn, select and trigger the expansion of a population of idiotypebearing T cells. Therefore, the expression of these T-cell idiotypic determinants must depend upon the presence of B cells or their products.More recently, we have tested this hypothe...

B cells are not essential for peripheral T-cell tolerance.

“…lb). These results are similar to those generated earlier in ,u-chain suppressed mice (29)(30)(31)(32)(33)(34).…”

The BALB/c Mouse

“…A similar shift in PHA responsiveness of splenic lymphocytes was not observed for the C3H/HeN and A/J (unpublished results) or C57BL/lO ScN mice (Damrow et al 1985); (iii) while the ability of splenic lymphocytes from saline injected mice to respond to ConA and PHA was preserved within the BALB/c sublines, the ability of CAL-20 splenic lymphocytes to respond to LPS-Ec was significantly less than CB-20 and the BALB/c sublines. The results of other studies show that the Igh genotype influences the immunoregulatory role of Band T cells and their products (Hayglass et al 1985). In our studies the generation of in vitro lymphocyte proliferative responses to mitogens and specific antigens either before or after WCV-I injection also seem to be influenced by Igh genotype.…”

CD4+T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools

“…Early studies using chronic treatment with anti-IgM to deplete B cells, and two recent studies with Ϫ/Ϫ mice, collectively support the notion that the presence of B cells is necessary for the normal functional development of T cells (20)(21)(22)(23)(24)(25)(26)(27). The earlier work suggests that certain T cells necessary for antibody production are absent from anti-IgM-treated mice, whereas the two most recent studies demonstrate the inability of T cells from Ϫ/Ϫ mice to produce normal levels of various cytokines in response to infection with lymphocytic choriomeningitis virus (21) and to protein immunization (20).…”