The Journal of Immunology, Vol 146, Issue 3 846-853, Copyright © 1991 by American Association of Immunologists

ARTICLES

Activation of dense human tonsilar B cells. Induction of c-myc gene expression via two distinct signal transduction pathways

MW White, F McConnell, GL Shu, DR Morris and EA Clark
Department of Biochemistry, University of Washington, Seattle 98195.

Antibodies to surface Ig or to the B cell marker CD20 trigger resting human B cells in similar yet distinct ways. Either antibody induces five-fold increases in the expression of the protooncogene, c-myc, as detected with semi-quantitative Northern blot assays. The induction of c-myc mRNA by anti-IgM or anti-CD20 is blocked by inhibitors of protein kinase C (PKC) such as staurosporine and by pretreatment of B cells with phorbol esters to reduce cellular PKC levels. This suggests that PKC is involved in the pathways stimulated by both anti-IgM and anti- CD20. However, anti-CD20, unlike anti-IgM, does not activate significant increases in inositol triphosphate or intracellular-free calcium. Further, anti-CD20-triggered elevation of c-myc mRNA is inhibited by pertussis and cholera toxins, whereas the pathway initiated by anti-IgM if anything is stimulated by pertussis toxin and unchanged by cholera toxin. Further differences in the nature of these two signals were seen when the expression of adhesion/recognition molecules were examined. Anti-IgM consistently induces increased expression of the adhesion molecules CD54 (I-CAM-1) and B7/BB-1 on B cells, but anti-CD20 does not. Yet both anti-CD20 and anti-IgM increase class II MHC, CD18 (LFA-1 beta-chain) and LFA-3 levels. These data suggest that the way in which B cells are activated may influence their surface phenotype and possibly subsequent migration or cell-cell interactions.

This article has been cited by other articles:

				G. Cartron, H. Watier, J. Golay, and P. Solal-Celigny From the bench to the bedside: ways to improve rituximab efficacy Blood, November 1, 2004; 104(9): 2635 - 2642. [Abstract] [Full Text] [PDF]

				D. Donati, L. P. Zhang, Q. Chen, A. Chene, K. Flick, M. Nystrom, M. Wahlgren, and M. T. Bejarano Identification of a Polyclonal B-Cell Activator in Plasmodium falciparum Infect. Immun., September 1, 2004; 72(9): 5412 - 5418. [Abstract] [Full Text] [PDF]

				J. Uchida, Y. Lee, M. Hasegawa, Y. Liang, A. Bradney, J. A. Oliver, K. Bowen, D. A. Steeber, K. M. Haas, J. C. Poe, et al. Mouse CD20 expression and function Int. Immunol., January 1, 2004; 16(1): 119 - 129. [Abstract] [Full Text] [PDF]

				M. J. Polyak and J. P. Deans Alanine-170 and proline-172 are critical determinants for extracellular CD20 epitopes; heterogeneity in the fine specificity of CD20 monoclonal antibodies is defined by additional requirements imposed by both amino acid sequence and quaternary structure Blood, May 1, 2002; 99(9): 3256 - 3262. [Abstract] [Full Text] [PDF]

				S. Mathas, A. Rickers, K. Bommert, B. Dörken, and M. Y. Mapara Anti-CD20- and B-cell Receptor-mediated Apoptosis: Evidence for Shared Intracellular Signaling Pathways Cancer Res., December 1, 2000; 60(24): 7170 - 7176. [Abstract] [Full Text]

				J. Golay, L. Zaffaroni, T. Vaccari, M. Lazzari, G.-M. Borleri, S. Bernasconi, F. Tedesco, A. Rambaldi, and M. Introna Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis Blood, June 15, 2000; 95(12): 3900 - 3908. [Abstract] [Full Text] [PDF]