Journal of Autoimmunity (1999) 12, 13–25 Article No. jaut.1998.0251, available online at http://www.idealibrary.com on Diversity of the B Cell Repertoire to Myelin Basic Protein in Rat Strains Susceptible and Resistant to EAE Ana Claudia Figueiredo, Irun R. Cohen and Felix Mor Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel Received: 29 June 1998 Accepted 20 October 1998 Myelin basic protein (MBP) is a major protein of central nervous system myelin which can induce experimental autoimmune encephalomyelitis (EAE) in susceptible laboratory animals. The role of T cells in the induction of EAE has been extensively studied, but the antibody response to MBP has not been well characterized. In the present work, we immunized rats with encephalito- genic guinea-pig MBP and mapped autoreactive antibodies binding to peptides in the rat MBP sequence. We studied the responses of the Lewis rat strain, susceptible to EAE, and the responses of the Fischer and Brown– Norway (BN) rats, resistant to EAE. We found that Lewis rats immunized to guinea-pig MBP develop antibodies to a diversity of MBP epitopes with a dominance of MBP peptide p11–30 and peptides in the 71–140 region. Fischer rats showed a similar pattern of antibody specificities, but with higher titers than the Lewis rats. BN rats, in contrast, developed a very low titer of antibodies and lacked a response to p11–30. Thus, there is no clear correlation between the nature of the anti-MBP antibody response and the state of susceptibility or resistance to EAE induction in the different rat strains. © 1999 Academic Press Key words: antibody repertoire, encephalomyelitis, myelin basic protein, rat Introduction Experimental autoimmune encephalomyelitis (EAE) is considered a prototype T cell-mediated auto- immune disease [1]. The current concept of the patho- physiology of EAE proposes that T cells specific for an autoantigen: myelin basic protein (MBP), proteolipid protein (PLP) or other neuroantigens, are activated in the periphery, migrate to the central nervous system and cause autoimmune inflammation leading to paralysis of the experimental animal [2]. Since it was demonstrated that MBP-specific T cell clones could transfer EAE [3], most of the experimental work on EAE has focused on the role of T cells. Immunization of experimental animals with MBP is known to lead to the production of anti-MBP anti- bodies. The dimensions of the B cell repertoire acti- vated in response to MBP immunization have not been well characterized. Most papers have focused on the B cell response to encephalitogenic determinants seen by T cells [4–6] with little analysis of the anti- body response to other regions of MBP. In multiple sclerosis, a recent analysis of antibodies eluted from brain tissue has pointed to a very restricted and similar range of B and T cell epitopes [7]. Antibodies are thought by most workers not to play a pathogenic role in the induction of EAE; antibodies alone cannot transfer the disease [8, 9], and there is no direct correlation between antibody titers and disease severity [10]. However, anti-MOG antibodies are known to mediate demyelination when given with encephalitogenic T cells [11]. Thus, some authors suggest that there is a synergy between T and B cells in the induction of EAE. In support of this concept, mice and rats depleted of B cells are resistant to dis- ease induction by MBP immunization [12, 13]. Other investigators have presented evidence for a protective role for anti-MBP antibodies; serum collected from animals recovered from EAE has been demon- strated to passively transfer resistance to EAE in naı ¨ve recipients [14, 15]. In the present work, we mapped the anti-MBP B cell repertoire in Lewis rats immunized with encephalito- genic guinea-pig MBP in CFA (MBP/CFA), using a panel of 17 synthetic overlapping peptides covering the amino acid sequence of the 18.5 kDa isoform of the rat MBP self-antigen. In addition, to uncover a poss- ible role of the anti-MBP antibody response in the development of EAE, we compared the anti-MBP antibodies elicited using a protocol leading to EAE in Lewis rats (MBP/CFA) to a protocol that does not result in disease (MBP/IFA). The same analysis was also performed in Fischer and BN rats, which do not develop EAE in response to guinea-pig MBP/CFA. We found that the B cell repertoire to MBP is diverse Correspondence: Prof Irun Cohen, Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel. Fax: 972–8–9344103. 13 0896–8411/99/010013+13 $30.00/0 © 1999 Academic Press