Work

The p65 Subunit of NF-κB Is Redundant with p50 During B Cell Proliferative Responses, and Is Required for Germline CH Transcription and Class Switching to IgG3

Year: 1999

Type: article

Abstract: B cells lacking individual NF-κB/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 γ3 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 (αδ-dex), B cells lacking both p50 and p65 exhibited severely impaired proliferation in response to LPS, αδ-dex, and CD40L. This defect could be overcome by simultaneous administration of αδ-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-κB in germline CH gene expression as well as functional redundancy between p50 and p65 during proliferative responses.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.162.4.1941