Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization.
Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.
Yu
W
W
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA.
Nagaoka
H
H
Jankovic
M
M
Misulovin
Z
Z
Suh
H
H
Rolink
A
A
Melchers
F
F
Meffre
E
E
Nussenzweig
M C
MC
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015322:Gene Rearrangement, B-Lymphocyte; D018858:Germinal Center / Q000166:cytology; D049452:Green Fluorescent Proteins; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D019891:Leukopoiesis / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008164:Luminescent Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D049452:Green Fluorescent Proteins; D015847:Interleukin-4