International Immunology Advance Access originally published online on March 13, 2008
International Immunology 2008 20(5):645-657; doi:10.1093/intimm/dxn021
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Requirements for the natural killer cell-mediated induction of IgG1 and IgG2a expression in B lymphocytes
1 Laboratory of Molecular Pathology, Department of Molecular Pathology
2 Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Correspondence to: D. Yuan; E-mail: dorothy.yuan{at}utsouthwestern.edu
Upon interaction with resting B lymphocytes, IL-2-propagated NK cells can initiate the process of Ig constant region switch recombination (CSR) by inducing germ line transcripts for
2a (I
2a) as well as increased levels of mRNA for activation-induced cytidine deaminase enzyme. Whereas both these processes are necessary for CSR, they are not sufficient because the cells do not proceed to the expression of mature mRNA for
2a (VDJC
2a). In addition, NK cells can also upregulate mRNA for the T-box transcription factor (T-bet) in B cells without being able to induce further differentiation. Using transgenic B cells with B cell receptor specificity for nitrophenol (NP), we have now shown that NP–Ficoll-stimulated B cells can be induced by NK cells to express IgG2a as well as IgG1 presumably due to the completion of the process of switch recombination. The inductive ability of NK cells does not require IFN-
but does require signals transmitted via CD48 by direct cell contact. In addition, NP–Ficoll on its own can induce proliferation of antigen-specific B cells as well as germ line transcripts of
1; however, expression of VDJC
1 mRNA also requires NK cell interaction with B lymphocytes. Therefore, in the presence of antigen, NK cells can provide a necessary signal that substitutes for cytokines in the induction of IgG2a as well as IgG1 expression. This in vitro analysis provides a mechanistic basis for understanding the documented NK cell effects on T-independent B cell responses in vivo.
Keywords: TI-II antigen, T-bet, CSR, circular transcripts, proliferation
Transmitting editor: G. Trinchieri
Received 13 September 2007, accepted 12 February 2008.