Repertoire restriction of immunoglobulin DH gene segments impairs T cell regulation of a thymus-dependent immune response (62.7)

Abstract

Abstract The significance of DH gene segments for the thymus-dependent (TD) immune response to the hapten 2-phenyloxazolone (phOx) was investigated in two mouse strains with a single DH gene segment that was derived from a modified DFL16.1 gene. In DD-DmuFS and in DD-iD mice, the central portion of the altered DH gene segment predominantly encodes for hydrophobic or charged amino acids, respectively. Compared with the response of BALB/c wild-type mice, the restriction of DH repertoire in both mutant strains caused drastic changes of the anti-phOx response. (i) The humoral anti-phOx antibody response was significantly reduced. (ii) Class switch recombination (CSR) was severely impaired. (iii) There was no restriction of VH/VL gene usage during CSR in the primary response and during further immune maturation. (iv) There was no selection of a dominant clonotype. (v) CSR did not select B cell clones with shorter and more uniform CDR-H3 lengths, as observed in BALB/c wild-type mice. These data confirm those obtained in wild-type mice and corroborate the view that CDR-H3-directed T cell action is important for clonal selection during CSR and immune maturation.