title: The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3.
abstract: B cells lacking individual NF-kappa B/Rel family members exhibit defects in activation programs. We generated small resting B cells lacking p65 or p50 alone, or lacking both p50 and p65, then evaluated the ability of these cells to proliferate, secrete Ig, and undergo Ig class switching. B cells lacking p65 proliferated well in response to all stimuli tested. However, these cells demonstrated an isolated defect in switching to IgG3, which was associated with a decrease in gamma 3 germline CH gene expression. Whereas, previously reported, B cells lacking p50 alone had a severe proliferative defect in response to LPS, a moderate defect in response to CD40 ligand (CD40L), and normal proliferation to Ag receptor cross-linking using dextran-conjugated anti-IgD Abs (alpha delta-dex), B cells lacking both p50 and p65 exhibited severely impaired proliferation in response to LPS, alpha delta-dex, and CD40L. This defect could be overcome by simultaneous administration of alpha delta-dex and CD40L. In response to this latter combination of stimuli, B cells lacking both p50 and p65 secreted Ig and underwent isotype switching to IgG1 as efficiently as B cells lacking p50 alone. These data demonstrate a role for the p65 subunit of NF-kappa B in germline CH gene expression as well as functional redundancy between p50 and p65 during proliferative responses.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Horwitz
authors.forename: P
authors.initials: P
authors.lastname: Zelazowski
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: K M
authors.initials: KM
authors.lastname: Wolcott
authors.forename: M L
authors.initials: ML
authors.lastname: Scott
authors.forename: D
authors.initials: D
authors.lastname: Baltimore
authors.forename: C M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000276:immunology*