The Journal of Immunology, Vol 135, Issue 6 3795-3801, Copyright © 1985 by American Association of Immunologists

ARTICLES

The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle

JT Golay, EA Clark and PC Beverley

Two monoclonal antibodies, 1F5 and B1, directed against the CD20 (Bp35) antigen were found to have both stimulatory and inhibitory effects on B cells. 1F5, but not B1, induces small resting tonsillar B cells and prolymphocytic leukemia cells to enlarge, to rapidly increase their RNA synthesis, and to become responsive to growth factors present in mixed lymphocyte reaction supernatants. In addition, 1F5 induces a moderate increase in thymidine uptake, which is accompanied by enhanced viability of the cells, but not by any increase in total cell number or by any detectable entry into S phase or mitosis. Taken together, these observations suggest that 1F5 can initiate transition from the G0 to the G1 phase of the cell cycle. The fact that all the changes observed can be inhibited by low concentrations (I50 = 50 ng/ml) of cyclosporin A is further evidence that 1F5 is involved at an early stage of B cell activation. Because both 1F5 and B1 belong to the IgG2a subclass, differences in their activities are likely to reflect their different epitope specificities. Although only 1F5 had stimulatory activity, both 1F5 and B1 strongly inhibited B cell differentiation to immunoglobulin secretion. Possible explanations for the dual activities of 1F5 and implications for the role of the CD20 antigen in B cell differentiation are discussed.

This article has been cited by other articles:

				N. S. Kapadia, J. M. Engles, and R. L. Wahl In Vitro Evaluation of Radioprotective and Radiosensitizing Effects of Rituximab J. Nucl. Med., April 1, 2008; 49(4): 674 - 678. [Abstract] [Full Text] [PDF]

				J. L. Teeling, W. J. M. Mackus, L. J. J. M. Wiegman, J. H. N. van den Brakel, S. A. Beers, R. R. French, T. van Meerten, S. Ebeling, T. Vink, J. W. Slootstra, et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20 J. Immunol., July 1, 2006; 177(1): 362 - 371. [Abstract] [Full Text] [PDF]

				N. Zhang, L. A. Khawli, P. Hu, and A. L. Epstein Generation of Rituximab Polymer May Cause Hyper-Cross-linking-Induced Apoptosis in Non-Hodgkin's Lymphomas Clin. Cancer Res., August 15, 2005; 11(16): 5971 - 5980. [Abstract] [Full Text] [PDF]

				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]

				A. J. Olszewski and M. L. Grossbard Empowering Targeted Therapy: Lessons from Rituximab Sci. Signal., July 13, 2004; 2004(241): pe30 - pe30. [Abstract] [Full Text] [PDF]

				R J Looney, J Anolik, and I Sanz B lymphocytes in systemic lupus erythematosus: lessons from therapy targeting B cells Lupus, May 1, 2004; 13(5): 381 - 390. [Abstract] [PDF]

				C. Berger, C. A. Blau, M.-L. Huang, J. D. Iuliucci, D. C. Dalgarno, J. Gaschet, S. Heimfeld, T. Clackson, and S. R. Riddell Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model Blood, February 15, 2004; 103(4): 1261 - 1269. [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]

				N. Di Gaetano, E. Cittera, R. Nota, A. Vecchi, V. Grieco, E. Scanziani, M. Botto, M. Introna, and J. Golay Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo J. Immunol., August 1, 2003; 171(3): 1581 - 1587. [Abstract] [Full Text] [PDF]

				A. Tzankov, J. Krugmann, F. Fend, M. Fischhofer, R. Greil, and S. Dirnhofer Prognostic Significance of CD20 Expression in Classical Hodgkin Lymphoma: A Clinicopathological Study of 119 Cases Clin. Cancer Res., April 1, 2003; 9(4): 1381 - 1386. [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. Alas, C. Emmanouilides, and B. Bonavida Inhibition of Interleukin 10 by Rituximab Results in Down-Regulation of Bcl-2 and Sensitization of B-cell Non-Hodgkin's Lymphoma to Apoptosis Clin. Cancer Res., March 1, 2001; 7(3): 709 - 723. [Abstract] [Full Text]

				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]

				M. J. Polyak, S. H. Tailor, and J. P. Deans Identification of a Cytoplasmic Region of CD20 Required for Its Redistribution to a Detergent-Insoluble Membrane Compartment J. Immunol., October 1, 1998; 161(7): 3242 - 3248. [Abstract] [Full Text] [PDF]

				J. P. Deans, S. M. Robbins, M. J. Polyak, and J. A. Savage Rapid Redistribution of CD20 to a Low Density Detergent-insoluble Membrane Compartment J. Biol. Chem., January 2, 1998; 273(1): 344 - 348. [Abstract] [Full Text] [PDF]

				J. P. Deans, L. Kalt, J. A. Ledbetter, G. L. Schieven, J. B. Bolen, and P. Johnson Association of 75/80-kDa Phosphoproteins and the Tyrosine Kinases Lyn, Fyn, and Lck with the B Cell Molecule CD20 J. Biol. Chem., September 22, 1995; 270(38): 22632 - 22638. [Abstract] [Full Text] [PDF]

				M. K. H. S. Hideo Mogami, and Itaru Kojima and M. Kanzaki Expression of Calcium-permeable Cation Channel CD20 Accelerates Progression through the G[IMAGE] Phase in Balb/c 3T3 Cells J. Biol. Chem., June 2, 1995; 270(22): 13099 - 13104. [Abstract] [Full Text] [PDF]