Role of MHC class II on memory B cells in post-germinal center B cell homeostasis and memory response.
We investigated the role of B cell Ag presentation in homeostasis of the memory B cell compartment in a mouse model where a conditional allele for the beta-chain of MHC class II (MHC-II) is deleted in the vast majority of all B cells by cd19 promoter-mediated expression of Cre recombinase (IA-B mice). Upon T cell-dependent immunization, a small number of MHC-II(+) B cells in IA-B mice dramatically expanded and restored normal albeit delayed levels of germinal center (GC) B cells with an affinity-enhancing somatic mutation to Ag. IA-B mice also established normal levels of MHC-II(+) memory B cells, which, however, subsequently lost MHC-II expression by ongoing deletion of the conditional iab allele without significant loss in their number. Furthermore, in vivo Ag restimulation of MHC-II(-) memory B cells of IA-B mice failed to cause differentiation into plasma cells (PCs), even in the presence of Ag-specific CD4(+) T cells. In addition, both numbers and Ag-specific affinity of long-lived PCs during the late post-GC phase, as well as post-GC serum affinity maturation, were significantly reduced in IA-B mice. These results support a notion that MHC-II-dependent T cell help during post-GC phase is not absolutely required for the maintenance of memory B cell frequency but is important for their differentiation into PCs and for the establishment of the long-lived PC compartment.
Shimoda
Michiko
M
Program in Molecular Immunology, Immunotherapy Center, Medical College of Georgia, Augusta, 30912, USA.
Li
Tao
T
Pihkala
Jeanene P S
JP
Koni
Pandelakis A
PA
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D000949:Histocompatibility Antigens Class II