Isotype commitment of B cells and dissemination of the primed state after mucosal stimulation with Mycoplasma pulmonis

Abstract

Live Mycoplasma pulmonis organisms were used to examine the immune response in the bronchus-associated lymphoid tissue after primary and secondary challenge with M. pulmonis, to study the dissemination of the primed state to distal tissues (i.e., spleen, peripheral blood, and Peyer's patches), and to determine whether the chronic antigenic stimulation accompanying infection influences the isotype potential and commitment of the primed B cells recovered from the various tissues. We have shown that exposure to M. pulmonis by a variety of routes results in a generalized rise in frequency of T-dependent, antigen-sensitive B cells in all lymphoid tissues. The route of secondary exposure to M. pulmonis was found to markedly increase the frequency of M. pulmonis-specific B cells in the bronchus-associated lymphoid tissue relative to that in the Peyer's patches after intraduodenal but not intratracheal challenge. A substantial rise in the number of M. pulmonis-sensitive B cells in the peripheral blood suggests that the dissemination of the primed state, at least in part, is due to B-cell migration via lymph and blood from local sites exposed to M. pulmonis. The majority of T-dependent clones generated by M. pulmonis-specific B cells secrete exclusively immunoglobulin G1 (IgG1). We have demonstrated that the exaggerated IgG1 response was not due to the accompanying viable donor T cells in the inoculum. The predominance of IgG1 was also demonstrated in clones from the bronchus-associated lymphoid tissue of athymic BALB/c mice that were primed with M. pulmonis. Thus, we can infer that functional T cells are not required for the development of specific B cells with the potential for IgG1 expression at the time of in vivo priming. When anti-trinitrophenyl- and anti-M. pulmonis-specific clones were generated in the same splenic fragment cultures stimulated by trinitrophenylated M. pulmonis, only the M. pulmonis-specific clones showed exaggerated IgG1 expression. Therefore, we conclude that the exaggerated IgG1 response accompanying M. pulmonis infection of euthymic mice seems to be dependent, at least in part, on an intrinsic property of the B cells that develop during this antigenic stimulation.