B cell intrinsic TLR signals amplify but are not required for humoral immunity.
Although innate signals driven by Toll-like receptors (TLRs) play a crucial role in T-dependent immune responses and serological memory, the precise cellular and time-dependent requirements for such signals remain poorly defined. To directly address the role for B cell-intrinsic TLR signals in these events, we compared the TLR response profile of germinal center (GC) versus naive mature B cell subsets. TLR responsiveness was markedly up-regulated during the GC reaction, and this change correlated with altered expression of the key adaptors MyD88, Mal, and IRAK-M. To assess the role for B cell-intrinsic signals in vivo, we transferred MyD88 wild-type or knockout B cells into B cell-deficient microMT mice and immunized recipient animals with 4-hydroxy-3-nitrophenylacetyl (NP) chicken gamma globulin. All recipients exhibited similar increases in NP-specific antibody titers during primary, secondary, and long-term memory responses. The addition of lipopolysaccharide to the immunogen enhanced B cell-intrinsic, MyD88-dependent NP-specific immunoglobulin (Ig)M production, whereas NP-specific IgG increased independently of TLR signaling in B cells. Our data demonstrate that B cell-intrinsic TLR responses are up-regulated during the GC reaction, and that this change significantly promotes antigen-specific IgM production in association with TLR ligands. However, B cell-intrinsic TLR signals are not required for antibody production or maintenance.
Seattle Children's Hospital Research Institute, Seattle, WA 98101, USA.
Almut
A
Meyer-Bahlburg
Socheath
S
Khim
David J
DJ
Rawlings
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D007107:Immune System; D051917:Leukosialin / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
D051917:Leukosialin; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors