CELLULAR IMMUNOLOGY 108,473-482 (1987) B-Cell Activation Stimulated by Monoclonal Anti-Lyb2.1 Antibody Is Mediated through a Receptor Distinct from the BSF-1 Receptor’ IEDA LAURINDO, FRED D. FINKELMAN, JENISHERO MIZUGUCHI,* AND JAMES J. MOND Department of Medicine, Uniformed Services University of the Health Sciences,4301 Jones Bridge Road, Bethesda, Maryland 20814, and *Laboratory of Immunology, National Institutes of Health, Bethesda, Maryland 20814 Received March 30, 1987; acceptedMay 8,1987 The experiments in this paper demonstrate that monoclonal anti-Lyb2.1 antibody enhances the proliferative response of anti-immunoglobulin (anti-I&stimulated but not of dextran sul- fate-stimulated B cells. The magnitude of this enhanced B-cell proliferation is comparable to that induced by BSF- 1 on anti-Ig-stimulated cells. The ability of this antibody to enhance B-cell proliferation does not result from its ability to neutralize the suppressive effectson B-cell activa- tion that is mediated by the Fc fragment of anti-Ig antibody as it is equally as effective in enhanc- ing B-cell proliferative responsesstimulated by F(ab’)r fragments of anti-Ig. BSF-1 and Anti- Lyb2.1 appear to stimulate nonoverlapping pathways leading to B-cell activation since the en- hanced responses induced by the combination of BSF- 1 and anti-Lyb2.1 on anti-Ig-stimulated cells are additive even when maximum quantities of these activators are employed. There is also a marked difference in their activity on T cells; while BSF- 1 can enhance T-cell proliferation in synergy with phorbol ester, anti-Lyb2.1 is ineffective in this regard. These data, while consistent with the suggestion that the Lyb2 surface determinant on B cells may be involved in B-cell activation, indicate that it is distinct from the receptors for BSF- 1 or BCGF-II. o 1987 Academic Press,Inc. INTRODUCTION Investigation into the mechanism of lymphokine-dependent B-cell activation has been greatly facilitated by the recent development of purified growth factors which influence B-cell growth. Although it has been known for some time that stimulation of B cells to proliferate or differentiate into antibody-secreting cells is dependent on the presenceof many T-cell-derived lymphokines ( l-7) the precise role of these solu- ’ This work was supported in part by CNPg-Brazil, Uniformed ServicesUniversity of the Health Sciences ResearchGrant Nos. R08347 and RO8308, Office ofNaval ResearchNO0014WR30341, National Insti- tutes of Health RO 1 AI2 1328, Armed Forces Radio biology Research Institute 840026, USAF FQ7624- 86-00017, and Office of Naval Research (G28353) NOOOl4-83-WR30341. The opinions or assertions contained herein are the private ones of the author(s) and are not to be construed as official or retlecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. The experiments reported herein were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals,” Institute of Animal Resources, National Research Council, DHEW Publ. No. (NIH) 78-23. 473 0008-8749187$3.00 Copyright 8 1987 by Academic F’res, Inc. All rights of reproduction in any form reserved.