The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline C-H transcription and class switching to IgG3

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 ce lls to proliferate, secrete Ig, and undergo Ig class switching, B cells lac king p65 proliferated well In response to all stimuli tested, However, thes e cells demonstrated an isolated defect in switching to IgG3, which was ass ociated with a decrease in gamma 3 germline C-H gene expression. Whereas, p reviously reported, B cells lacking p50 alone had a severe proliferative de fect in response to LPS, a moderate defect in response to CD40 Ligand (CD40 L), and normal proliferation to Ag receptor cross-linking using dextran-con jugated anti-IgD Abs (alpha delta-dex), B cells tacking both p50 and p65 ex hibited severely impaired proliferation in response to LPS, alpha delta-dex , and CD40L, This defect could be overcome by simultaneous administration o f alpha delta-dex and CD40L. In response to this latter combination of stim uli, B cells tacking both p50 and p65 secreted Ig and underwent isotype swi tching to IgG1 as efficiently as B cells lacking p50 alone, These data demo nstrate a role for the p65 subunit of NF-kappa B in germline C-H gene expre ssion as well as functional redundancy between p50 and p65 during prolifera tive responses.