B cells lacking RelB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching.
A number of distinct functional abnormalities have been observed in B cells derived from p50/ NF-kappa B or c-rel knockout mice. RelB, another member of the NF-kappa B/Rel family of transcription factors, is expressed during the latter stages of B cell maturation and can bind to regulatory sites within the Ig heavy chain locus. Therefore, we tested the ability of B cells from relB knockout mice (relB-/-) to proliferate, undergo maturation to IgM secretion, and switch to the expression of downstream Ig isotypes in response to distinct activators including LPS, anti-CD40 mAb or CD40 ligand, and/or dextran anti-IgD antibodies in combination with various cytokines, including IL-4, IL-5, IFN-gamma, and TGF-beta. B cells lacking RelB showed up to 4-fold reductions in DNA synthesis in response to LPS, CD40, and membrane Ig-dependent activation relative to controls. However, relB-/- B cells were comparable to control B cells in their ability to undergo maturation to IgM secretion and switch to the expression of IgG3, IgG1, IgG2b, IgG2a, IgE, and/or IgA under all activation conditions tested. Thus, RelB, like c-Rel and p50/NF-kappa B, plays a role in B cell proliferation. However, in contrast to c-Rel and p50/ NF-kappa B, it is not critically involved in maturation to Ig secretion or expression of Ig isotypes.
Snapper
C M
CM
Department of Pathology, Uniformed Services, Bethesda, Maryland 20814, USA.
Rosas
F R
FR
Zelazowski
P
P
Moorman
M A
MA
Kehry
M R
MR
Bravo
R
R
Weih
F
F
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency
D000906:Antibodies; D019013:CD40 Antigens; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors