Regulatory Role of Peritoneal B Cells in EAE

Abstract

B cells play a dual role in the pathogenesis of autoimmune diseases. In experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis, B cells contribute to disease progression, while their regulatory role predominates in the initial phases of disease development. Several studies have identifi ed diff erent subsets of regulatory B cells, mostly in the spleen SAŽETAK B limfociti imaju dvojnu ulogu u patogenezi autoimunskih bolesti. B limfociti doprinose progresiji eksperimentalnog autoimunskog encefalomijelitisa(EAE), eksperimentalnog modela za multiplu sklerozu, a u inicijalnim fazama razvoja bolesti dominira njihova regulatrona uloga. U nekoliko studija je identifi kovano nekoliko subpopulacija regulatornih B limfocita, uglavnom u slezini, a sve produkuju IL-10. Međutim i peritonealni B limfociti produkuju IL-10, migriraju ka infl amatornim stimulusima i mogu da imaju imunoregulatornu funkciju. Pošto smo uočili ekspanziju regulatornih B limfocita u peritoneumu miševa rezistentnih na indukciju EAE, ovde razmatramo regulatorne uloge B limfocita u patogenezi EAE i moguću ulogu peritonealnih regulatornih B limfocita u rezistenciji na indukciju EAE. Ključne reči: multipla skleroza, EAE, B limfociti, peritonealni regulatorni B limfocitiB cells are effector cells of the adaptive humoral immune system that act by producing specific antibodies. However, B cells express numerous innate immune receptors, including Toll-like receptor (TLR)-3, TLR4, TLR7, TLR8 and TLR9 (1,2); stimulation of these receptors also induces antibody production. It is well established that two populations of B cells exist-B1 and B2 cells-that can be distinguished according to their phenotype, ontogeny, anatomical location and function (3-5). B2 cells, which include follicular and marginal zone B cells, originate from bone marrow precursors and circulate throughout the blood and secondary lymphoid tissues. These cells respond to a broad range of T-dependent and T-independent antigens. In contrast to B2 cells, B1 cells develop during foetal and neonatal develop-REVIEW PAPER REVIJALNI RAD REVIEW PAPER REVIJALNI RAD REVIEW PAPER ment, have the capacity to self-renew, and predominantly localize to peritoneal and pleural cavities (3-5). B1 cells are innate immune cells that produce the majority of "natural" immunoglobulins, which are encoded by germline immunoglobulin genes. These natural immunoglobulins act as a first line of defence against pathogens, such as encapsulated polysaccharide-expressing bacteria (4, 5). There are two functionally distinct subsets of B1 cells that can be delineated by differential expression of CD5 (4). B1 cells that express CD5 are known as B1a cells, and those that lack CD5 expression, but have other hallmarks of B1 cells, are known as B1b cells. CD5 + peritoneal B1a cells produce an abundance of interleukin-10 (IL-10) following stimulation with TLR agonists, such as lipopolysaccharide (LPS) (6).