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B cells from p50/NF-κB knockout mice have selective defects in proliferation, differentiation, germ-line C_H transcription, and Ig class switching

Snapper, Clifford M. and Zelazowski, Piotr and Rosas, Fabio R. and Kehry, Marilyn R. and Tian, Ming and Baltimore, David and Sha, William C. (1996) B cells from p50/NF-κB knockout mice have selective defects in proliferation, differentiation, germ-line C_H transcription, and Ig class switching. Journal of Immunology, 156 (1). pp. 183-191. ISSN 0022-1767.

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To better understand the role of NF-κB in normal B cell physiology, we used a purified population of resting B cells from p50/NF-κ B knockout (p50^(-/-)) mice to determine their ability to proliferate, secrete Ig, express germ-line C_H RNA, and undergo Ig isotype switching in vitro in response to a number of distinct stimuli. p50^(-/-) B cells proliferated normally in response to dextran-anti-IgD Abs (αδ-dex) and membrane-bound, but not soluble, CD40 ligand (CD40), and they were virtually unresponsive to LPS when compared with control B cells. p50^(-/-) B cells secreted markedly reduced Ig in response to αδ-dex or mCD40L in the presence of IL-4 + IL-5, despite their relatively normal proliferative rates, whereas normal Ig secretion was restored by the combination of αδ-dex and CD40L. p50^(-/-) B cells expressed normal steady-state levels of germ-line C_Hγ1 and C_Hα RNA but markedly reduced germ-line C_Hγ3 and C_Hϵ RNA upon appropriate stimulation. Although p50^(-/-) B cells underwent substantial switching to IgG1, a marked reduction in the switch to IgG3 and IgE, as IgA, was observed. These data are the first to demonstrate key, independent roles for p50/NF-κB in normal B cell maturation to Ig secretion, germ-line CH gene activation, and Ig class switching, as well as mitogenesis, and provide a powerful and well-defined in vitro model system for studying the role of p50/NF-κB in a wide range of normal cellular functions.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 by The Amerlcan Association of Immunologists. Received for publication August 7, 1995. Accepted for publication October 26, 1995. We thank Drs. James Mond, Fred Alt, Janet Stavnezer, and Barbara Birshtein for helpful discussions. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103078
Deposited By: Tony Diaz
Deposited On:08 May 2020 17:50
Last Modified:08 May 2020 17:50

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