The Importance of CD5-Positive B Cells in Nonorgan-Specific Autoimmune Diseases

Abstract

CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CDS-expressing B cells is increased in patients withrheumatoid arthritis or primaIy Sjogren's syndrome. These cells are similar to those leading to chronic lymphocytic leukemia (they may be induced to produce multispecific autoantibodies). Multispecific autoantibodies have also been described in the early B cell repertoire.The human 67 kD glycoprotein termed CD5 (1) is equivalent to Ly 1 in the mouse (2). This molecule has originally been described as a pan-T marker (3), then found on some B cell tumors (4), particularly chronic lymphocytic leukemia (CLL) of the B-cell type, and finally demonstrated ( fig. 1) on a minute proportion of normal B lymphocytes (5). Evidence has been accumulating suggesting that the B cells carrying this marker would play a key-role as producers of antibodies to nonorgan-specific self constitutents and antibodies to idiotypes broadly expressed by these autoantibodies.On this assumption, three sets of observations will be discussed in this paper. Firstly, the frequency of circulating CD5-positive B cells is increased in nonorgan-specific autoimmune diseases, such as rheumatoid arthritis (RA) and primary Sjdgren's syndrome (SS). Secondly, CLL may be regarded as a model to investigate the CDS+B cells, since this marker was found to be expressed on virtually all the malignant B clones (6) and the lymphocytes may be induced to secrete autoantibodies. Thirdly, the early B cell repertoire, enriched in the CD5 subset (7), contains IgM antibodies which react with at least one autoantigen screened for. The frequency of circulating CD5-positive B cells is increased in nonorgan-specific autoimmune diseasesCD5 molecules are barely detectable on a minority of normal circulating B lymphocytes, when the cells are examined using a fluorescence microscope. We have therefore improved the sensitivity of their detection (8) by treating the B cell-enriched preparation with phorbol myristic acetate (PMA), a tumour-promoting agent. After 48 hour-incubation with PMA, the percentage of CDS+B cells increased in tonsil, lymph node, spleen and blood B cells Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/01/14 For personal use only. Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/01/14 For personal use only. Scand J Rheumatol Downloaded from informahealthcare.com by Mcgill University on 12/01/14 For personal use only. La1 S, Lydyard PM. Chronic fymphaytic leukemia cells secrete mkkpec@c autwntibodies. J Autoimmunity 1988; 13469-81. 21. Logtenberg T, Kroon A, Gmelig-Meyling FHJ, Ballieux RE.Anafysk of the / m a n twtsil B cell reprtoire by somatic hybridizntion: occurrence of both " m m p c $ c " and "mltispeCi,Fc" {auto) antibody-secreting cells. Eur J Immunol1987; 17855-9. 22. Dighiero G, Lymberi P, Mazie JC, Rouyre S, Butler-Browne GS, Whalen m, Avrameas S. Murine hybridom secretingnafurd mun...

Evidence for somatic selection of natural autoantibodies.

“…With regard to CLL, it is not certain whether the apparent selection for polyreactive autoreactivity merely reflects its cytogenesis, or if it actually plays a role in leukemogenesis (48,49). Recent studies indicate that most patients with CLL have leukemia cells that express IgM autoantibodies that, like the SMI transfectoma IgM~, react with a variety of different self antigens (3)(4)(5)(6). The frequency of CLL patients that have leukemia B cells that express such polyreactive autoantibodies apparently greatly exceeds the noted frequency of polyreactive B cells in normal embryonic tissues, cord blood or adult peripheral blood.…”

“…for human IgG (2). Subsequent studies demonstrated that over half of all CLL patients have leukemia cells that can be stimulated to secrete autoantibodies in vitro that bind to a variety of self-antigens, most notably human IgG (3)(4)(5)(6). Although each of the leukemia cell cultures in these studies was monoclonal, the secreted autoantibodies generally were polyspecific, each Ig binding to two or more distinct self-antigens, e.g., human IgG, ssDNA, dsDNA, histones, cardiolipin, actin, thyroglobulin, and/or cytoskeletal components.…”

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

“…Furthermore, it is known that elderly produce increased levels of antibodies to autologous antigens often accompanied by autoimmune phenomena (Candore et al, , 1997Banerjee et al, 2002) and are less able to make high-affinity antibodies to foreign antigens. Indeed, increased CD5 + B lymphocytes, that, as known, play a key role as producers of autoantibodies (Dalloul, 2009;Youinou et al, 1988), have been demonstrated in old humans (Weksler, 2000) and mice (Alter-Wolf et al, 2009b), in lupus mouse models (Zhong et al, 2009) and in human rheumatoid arthritis (Nakiri et al, 2007). However in our previous paper (Colonna Romano et al, 2003) we found an age-related decrease of CD5 + B cells, The intriguing aspect is that, in our elderly population, there is an increase of the IgD − CD27 − DN B cells, and one hypothesis might be that these cells could be responsible for production of autoantibodies or cytokines that lead to an imbalance of the mechanism controlling the immune response against self antigens.…”

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts

“…Although the origin of these soluble scavenger receptors in RA is poorly understood, it has been suggested that they are shed in the serum by proteases from the surface of activated lymphocytes that subsequently infiltrate synovium structures ( 40 ). In fact, increased serum levels of sCD5 and sCD6 has been found in subjects diagnosed with RA ( 41 – 44 ) but also other autoimmune diseases such as primary Sjögren’s syndrome ( 42 , 45 , 46 ), systemic inflammatory response syndrome ( 47 ), multiple sclerosis ( 44 ) or dermatitis ( 48 ). Although the functional role of both soluble scavengers in autoimmune diseases is still under investigation, it is well established that sCD5 and sCD6 are regulators of T cell functions and induce autoreactivity.…”