Immunoglobulin-specific T-B cell interaction. I. Presentation of self immunoglobulin determinants by B lymphocytes.
Academic Article
Overview
abstract
Immunoglobulin (Ig)-specific T-B cell interactions have been studied in the model of T cell recognition of the kappa chain Ig kappa-1b allotype in Ig kappa-1-congeneic rat strains. An efficient presentation of endogenous Ig allotypic determinants by irradiated spleen cells from (WAG.1b x August)F1 (RT-1u/c; Ig kappa-1b/1a) rats to Ig kappa-1b-specific lymph node T cells from Ig kappa-1-congeneic (WAG x August)F1 (RT-1u/c; Ig kappa-1a) rats was demonstrated. This presentation was found to be sensitive to high irradiation doses (greater than 1000 rad). By fractionation of Ig kappa-1b+ F1 spleen cells on Percoll density gradient we have shown that a radioresistant, low-density fraction, consisting mainly of macrophages (M phi) and dendritic cells, triggers only weak Ig kappa-1b-specific T cell response. The high level of response was observed against radiosensitive spleen cell fractions of intermediate and high density, suggesting that B cells were the main antigen-presenting cells (APC) of Ig kappa-1b determinants of endogenous Ig. This conclusion was confirmed in the experiments using purified B cells from Ig kappa-1b-bearing rats. Earlier we have shown that the responsiveness of August (RT-1c; Ig kappa-1a) and WAG (RT-1u; Ig kappa-1a) rats to Ig kappa-1b in vivo is controlled by the dominant allele of an RT-1-linked Ir gene. August and (August X WAG)F1 rats were found to be responders to Ig kappa-1b while WAG rats were nonresponders. The same pattern of Ir gene-controlled reactivity was demonstrated using an Ig kappa-1b-specific T cell proliferation assay. Ig kappa-1b-specific F1 T cell response was only observed when Ig kappa-1b+ B cells or IgG (Ig kappa-1b)-pulsed M phi-bearing responder major histocompatibility complex (MHC) haplotype were used as the APC. Anti-RT-1 monoclonal antibody inhibition studies suggested that the RT-1Bc molecule is the main restricting element of T cell recognition of Ig kappa-1b+ B cell as well as exogenous IgG (Ig kappa-1b). We have demonstrated allelic exclusion of Ig kappa-1b presenting function by negatively and positively selecting for Ig kappa-1b+ and Ig kappa-1a+ B cells from heterozygous F1(Ig kappa-1b/1a) rats. This clearly indicate that the B cells presented exclusively Ig kappa-1b allotypic determinants of their own Ig.(ABSTRACT TRUNCATED AT 400 WORDS)
