The T/B cell interaction involved in induction of the mouse IgG2a^h suppression is restricted by major histocompatibility complex class I, but not class II molecules

Abstract

To determine the major histocompatibility complex (MHC) restriction of the T/ B cell interaction involved in a negative regulation of Ig production, we used mouse model of T cell-induced IgG2ab suppression in vivo. Normal or specifically triggered T splenocytes from mice of the Igha haplotype, when neonatally transferred into histocompatible Igha/b heterozygotes, are able to induce a specific and total suppression of the IgG2ab allotype. Nevertheless, only transfer of IgG2ab-primed Igha T splenocytes induces this suppression in Ighb/b homozygous congenic mice in which the whole IgG2a isotype production is inhibited. This suppression is chronically maintained by CD8+ T cells, but can be experimentally reversed. We have established that the suppression induction required a CD4+CD8+ T cell cooperation and operated via the recognition by the involved TCR of C gamma 2ab-derived peptides presented by the target B cells in an MHC haplotype-restricted manner. Here, by using Ighb mice genetically deficient for MHC class I (beta 2-microglobulin%, or beta 2m%) or class II (I-A beta%) molecules, we demonstrate functionally that the suppression induction implicates an MHC class I-, but not class II-restricted interaction. Indeed, the anti-IgG2ab T cells transferred into Ighb H-2b I-A beta% mice carry out the suppression process normally, while in Ighb H-2b beta 2m% recipients, their suppression induction capacity is significantly inhibited. Moreover, the C gamma 2ab 103-118 peptide, identified as the sole C gamma 2ab-derived peptide able to amplify the anti-IgG2ab T cell reactivity in Igha H-2b mice, is also able to stabilize the H-2Db, but not the H-2Kb class I molecules at the surface of RMA-S (TAP2-, H-2b) cells. These results indicate that, despite the CD4+/CD8+ T cell cooperation during the induction phase of suppression only MHC class I molecule expression is required at the surface of IgG2ab+ B cells for suppression establishment.

Impaired NK1.1+ T cells do not prevent the development of an IgE‐dependent allergic phenotype

“…Therefore, the immune response for both strains has to be regarded as a mixed Th 0 response. Whether the higher levels of IgG2a in β 2 m−/− mice were due to the lack of MHC class I molecules as described elsewhere [ 16] was not further investigated.…”

The strength of B cell immunity in female rhesus macaques is controlled by CD8+T cells under the influence of ovarian steroid hormones

“…By contrast, we did not detect altered cytokine expression in progesterone‐stimulated CD8 + T cells, suggesting that these soluble mediators do not mediate the progesterone‐mediated decrease in ISC frequency. In mice, there are several models of Ig suppression due to MHC I‐restricted CD8 + T cell‐mediated lysis of B cells [38–42]. By analogy, the progesterone‐mediated decline in ISC cell frequency may be due to lysis of B cells by CD8 + T cells.…”

Central tolerance induction in natural immunoglobulin-allotype-specific T cells

“…The suppression-induction phase in T cell recipients requires cooperation between CD4 + and CD8 + T cells, both specific for IgG 2a b [14,15]. The suppression effectors are MHC class I-restricted, cytotoxic CD8 + T cells [16,17], which use, alternatively or concomitantly, perforin-and Fas-mediated pathways to continuously eliminate B cells committed to IgG 2a b production [18].…”