The Expression of CD45RB on Antigen-Responsive CD4 + Lymphocytes: Mouse Strain Polymorphism and Different Responses to Distinct Antigens

Abstract

The levels of CD45RB expression by HGG-specific CD4 + cells residing in the Ag-draining lymph nodes of HGG-primed CBA/CaJ mice were analyzed. When sorted populations of CD4 +, CD45RB hi, and CD4 +, CD45RB lo cells were cultured with HGG and Ag-presenting cells, the majority of the proliferative response was found in the CD45RB lo fraction early after in vivo priming (Day 6), and this pattern remained stable through 12 days postpriming. To determine whether this segregation of responsiveness was consistent in other mouse strains, HGG-primed C57BL/6J mice were similarly analyzed. In contrast to findings with the CBA/CaJ strain, the CD4 +, CD45RB hi cell fraction obtained from C57BL/6J mice was the predominant responding population early after in vivo priming (Day 6); however, there was a parallel increase in responsiveness of CD4 +, CD45RB hi, and CD4 +, CD45RB lo cells by Day 12. Thus, there was not a decrease in CD45RB hi expression with a concommitant increase in CD45RB lo expression in CD4 + cells proliferating to HGG. Despite the heterogeneity in CD45RB expression by the primed CD4 + cells of the two strains, the entire proliferative response to HGG early after priming resided in the fraction bearing high levels of membrane CD44, thus arguing for the existence of CD45RB hi, CD44 hi and CD45RB lo, CD44 hi cells during the early phase of the response. In both mouse strains the CD4 +, CD45RB hi subset of primed lymph node cells produced significant levels of IL-2 in response to HGG and APC, whereas no significant IL-2 or IL-4 production was detectable in HGG-stimulated CD45RB lo cells of either strain. The CD4 +, CD45RB hi subset also proliferated more vigorously in response to polyclonal activation than the CD4 + CD45RB lo fraction. To examine whether the patterns of CD45RB expression on HGG-primed cells from C57BL/6J mice were common to other antigens, the response profiles were examined after in vivo priming with a second antigen, KLH. In contrast to studies with HGG as the Ag, the proliferative response to KLH in C57BL/6J mice was evenly divided among the CD45RB hi and CD45RB lo fractions on Day 8 after priming, but shifted markedly to the CD45RB lo fraction by Day 12 after priming. Taken together, these data show that the patterns of CD45RB expression on primed populations of CD4 + cells can exhibit mouse strain polymorphism and can differ depending on the choice of antigen for immunization.