TLR agonists promote marginal zone B cell activation and facilitate T-dependent IgM responses.
Although IgM serves as a first barrier to Ag spreading, the cellular and molecular mechanisms following B lymphocyte activation that lead to IgM secretion are not fully understood. By virtue of their anatomical location, marginal zone (MZ) B cells rapidly generate Ag-specific IgM in response to blood-borne pathogens and play an important role in the protection against these potentially harmful Ags. In this study, we have explored the contribution of TLR agonists to MZ B cell activation and mobilization as well as their ability to promote primary IgM responses in a mouse model. We demonstrate that diverse TLR agonists stimulate MZ B cells to become activated and leave the MZ through pathways that are differentially dependent on MyD88 and IFN-alphabeta receptor signaling. Furthermore, in vivo stimulation of MZ B cells with TLR agonists led to a reduction in the expression of the sphingosine-1-phosphate (S1P) receptors expressed by MZ B cells and/or increased CD69 cell surface levels. Importantly, as adjuvants for a T cell-dependent protein Ag, TLR agonists were found to accelerate the kinetics but not magnitude of the Ag-specific IgM response. Together, these data demonstrate that in vivo TLR agonist treatment enhances the early production of Ag-specific IgM and activates MZ B cells to promote their relocation.
Rubtsov
Anatoly V
AV
Integrated Department of Immunology, University of Colorado Denver and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Swanson
Cristina L
CL
Troy
Scott
S
Strauch
Pamela
P
Pelanda
Roberta
R
Torres
Raul M
RM
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000502:physiology
D000276:Adjuvants, Immunologic; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D049349:Receptors, Lysosphingolipid; D051193:Toll-Like Receptors