CELLULAR IMMUNOLOGY 143, I 1-22 (1992) Role of CR2 in the Human Adult and Neonatal in Vitro Antibody Response to Type 4 Pneumococcal Polysaccharide ARJAN W. GRIFFIOEN, ELLY A. H. TOEBES, BEN J. M. ZEGERS, AND GER T. RIJKERS Dcpurtmenr o~‘lmm~mo/o~~. l!niversify Children :c Hospital, “He1 W’ilhelminu Kinder;iekenh~~is. ” P.O. Bo.x 18009, 3501 CA C’trecht. The Netherlunds Received Nwemher 13. 1991; uccepled April 20, 1992 A number of studies have indicated that the complement receptor type 2 (CR2), which is the receptor for C3d, a degradation fragment of the complement component C3, regulates B lymphocyte activation and growth. Early reports have described that C3 regulates T cell-dependent (TD) antibody responses, The involvement of CR2 in the antibody response to T cell-independent type 2 (TI-2) antigens was investigated because neonatal B cells. which are unresponsive to TI-2 antigens both in viva and in vitro, express a significantly decreased level of CR2 as compared to B cells of adult donors. We utilized type 4 pneumococcal polysaccharide (PS4) as a model TI-2 antigen. In order to study the relationship between CR2 and the response to PS4, B cells were costimulated with PS4 and monoclonal antibodies (MAb) to CR2. HB5 and OKB7 anti-CR2 monoclonal antibodies enhanced the in vifrn response of adult B cells to PS4, as measured in a PS4-specific spot-forming cell assay. Neonatal B cells could only be induced to respond to PS4 using high concentrations of OKB7 anti-CR2 MAb. The 8-mercaptoguanosine (8MGuo). an agent that can overcome the in vitro unresponsiveness to PS4 of neonatal B cells, increased CR2 expression on adult and neonatal B cells. Furthermore, XMGuo synergizes strongly with anti-CR2 antibodies in augmenting the anti-PS4 antibody response. Data presented in this report provide evidence of CR2 involvement in the antibody response to PS4 and that the neonatal B cell unresponsiveness to TI-2 antigens may be due to the decreased expression of CR2. W 1992 Academic Press. Inc INTRODUCTION It is well recognized that the complement system (C) plays a role in the regulation of the immune response (1). More recently the role of degradation fragments of com- plement components in T and B cell activation has been defined (2, 3). Early studies suggested that C3 might mediate T-B cooperation since depletion of C3 abrogated antibody responses to T cell-dependent (TD) but not to T cell-independent (TI) antigens (4, 5). However, subsequent studies provided evidence that also antibody responses to TI antigens could be impaired after prolonged depletion for C3 (6). In addition, C3-deficient dogs have defective antibody responses to TI antigens (7). It is probable therefore that complement receptors on B cells are involved in TD and TI antibody responses. Human B lymphocytes bear two distinct receptors for fragments of C3, both of which are involved in B cell activation (8). CR1 (CD35) recognizes the C3c region and binds C3b with high affinity and iC3b and C4b with lower affinity. B cell differentiation can be enhanced by antibodies against CR1 (9). CR2 (CD21) is a 145 kDa glycoprotein which is expressed on the majority of mature resting B cells and on II 0008-8749/92 $5.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.