Role of MHC Class II on Memory B Cells in Post-Germinal Center B Cell Homeostasis and Memory Response

• Published in: Journal of Immunology Vol. 176; no. 4; pp. 2122 - 2133
• Main Authors: Shimoda, Michiko, Li, Tao, Pihkala, Jeanene P. S, Koni, Pandelakis A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2006
• Subjects: Animals; Antigens - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Differentiation - immunology; Cell Proliferation; Germinal Center - cytology; Germinal Center - immunology; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Homeostasis; Immunologic Memory - immunology; Mice; Mice, Inbred C57BL; Phenotype; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.4.2122

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.