MyD88 is required for the formation of long-term humoral immunity to virus infection.
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.
Guay
Heath M
HM
Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Andreyeva
Tatyana A
TA
Garcea
Robert L
RL
Welsh
Raymond M
RM
Szomolanyi-Tsuda
Eva
E
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D027601:Polyomavirus Infections / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000502:physiology; D053724:Receptors, Interleukin-18 / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology; D019562:Viral Load
D000914:Antibodies, Viral; D007074:Immunoglobulin G; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18; D051193:Toll-Like Receptors