MyD88 is required for the formation of long-term humoral immunity to virus infection
Department of Pathology
Animals; Antibodies, Viral; B-Lymphocytes; Immunoglobulin G; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; Polyomavirus Infections; Receptors, Interleukin-1; Receptors, Interleukin-18; Signal Transduction; T-Lymphocytes; Toll-Like Receptors; Viral Load
Life Sciences | Medicine and Health Sciences
Development of long-term humoral immunity is a major goal of vaccination, but the mechanisms involved in the formation of long-term Ab responses are still being determined. In this study, we identify a previously unknown requirement for MyD88, an adaptor molecule that mediates signals at most TLRs, for the generation of long-term humoral immunity during live virus infection. Polyoma virus-infected MyD88 knockout mice generated strong acute T cell-dependent antiviral IgM and IgG responses and developed germinal centers. Activation-induced cytidine deaminase, an enzyme required for isotype switching and somatic hypermutation, was also induced in germinal center B cells, similar to wild-type mice. However, MyD88 knockout mice failed to develop bone marrow plasma cells and did not maintain long-term serum antiviral Ab responses. The isotype distribution of antiviral IgG responses was also altered; serum IgG2a and IgG2b levels were diminished, whereas IgG1 responses were not affected. The requirement for MyD88 for the formation of long-term humoral immunity to polyoma virus was intrinsic to B cells and was independent of IL-1R and IL-18R, cytokine receptors that also signal through MyD88. Our findings show that MyD88-dependent signaling pathways in B cells are essential for effectively generating long-term Ab responses and implicate a role for TLR in the formation of long-term humoral immunity.
DOI of Published Version
J Immunol. 2007 Apr 15;178(8):5124-31.
Journal of immunology (Baltimore, Md. : 1950)
Guay, Heath M.; Andreyeva, Tatyana A.; Garcea, Robert L.; Welsh, Raymond M.; and Szomolanyi-Tsuda, Eva, "MyD88 is required for the formation of long-term humoral immunity to virus infection" (2007). Open Access Articles. 1294.