Parameters governing exhaustion of rare T cell-independent neutralizing IgM-producing B cells after LCMV infection.
The late appearance of neutralizing antibodies (nAb) against lymphocytic choriomeningitis virus (LCMV) has been attributed to various factors including immunopathology, low frequency of high-affinity specific B cells and competition by nonspecific polyclonal B cell activation. To investigate the activation of LCMV-nAb-producing B cells early following infection, we performed adoptive transfers of LCMV-specific B cells into WT recipients. By modulating parameters such as viral load, number of specific B cells and presence of T cell help, we found that a high antigen-to-B cell ratio led to normal IgM responses. IgG and memory response however, were impaired as most nAb-producing B cells rapidly terminally differentiated into short-lived IgM plasma cells. Lowering the antigen-to-B cell ratio, or increasing the level of T cell help, could rescue the class-switched antibody response. Upon infection, a low frequency of LCMV-nAb-producing B cells, as observed in WT mice, results in a high antigen-to-B cell ratio and is likely to lead to terminal differentiation - and elimination - of these rare B cells.
Zellweger
Raphaël M
RM
Institute of Experimental Immunology, University Hospital Zürich, Zürich, Switzerland. raphael.zellweger@alumni.ethz.ch
Hangartner
Lars
L
Weber
Jacqueline
J
Zinkernagel
Rolf M
RM
Hengartner
Hans
H
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000502:physiology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000502:physiology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009500:Neutralization Tests; D051381:Rats; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M