Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells.
The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.
Laboratory of Molecular Immunology, The Rockefeller University, New York 10021-6399, USA.
E
E
Meffre
F
F
Papavasiliou
P
P
Cohen
O
O
de Bouteiller
D
D
Bell
H
H
Karasuyama
C
C
Schiff
J
J
Banchereau
Y J
YJ
Liu
M C
MC
Nussenzweig
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D014066:Palatine Tonsil / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011995:Recombination, Genetic
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004253:DNA Nucleotidylexotransferase