Cutting edge: An in vivo reporter reveals active B cell receptor signaling in the germinal center.
Long-lasting Ab responses rely on the germinal center (GC), where B cells bearing high-affinity Ag receptors are selected from a randomly mutated pool to populate the memory and plasma cell compartments. Signaling downstream of the BCR is dampened in GC B cells, raising the possibility that Ag presentation and competition for T cell help, rather than Ag-dependent signaling per se, drive these critical selection events. In this study we use an in vivo reporter of BCR signaling, Nur77-eGFP, to demonstrate that although BCR signaling is reduced among GC B cells, a small population of cells exhibiting GC light zone phenotype (site of Ag and follicular helper T cell encounter) express much higher levels of GFP. We show that these cells exhibit somatic hypermutation, gene expression characteristic of signaling and selection, and undergo BCR signaling in vivo.
Russel/Engleman Medical Research Center, Division of Rheumatology, University of California San Francisco, San Francisco, CA 94143.
James
J
Mueller
Russel/Engleman Medical Research Center, Division of Rheumatology, University of California San Francisco, San Francisco, CA 94143 julie.zikherman@ucsf.edu mehrdad.matloubian@ucsf.edu.
Mehrdad
M
Matloubian
Russel/Engleman Medical Research Center, Division of Rheumatology, University of California San Francisco, San Francisco, CA 94143 julie.zikherman@ucsf.edu mehrdad.matloubian@ucsf.edu.
Julie
J
Zikherman
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
D000941:Antigens; D011947:Receptors, Antigen, B-Cell