B-cell activation in patients with irritable bowel syndrome (IBS) L. O ¨ HMAN,*,  A.-C. LINDMARK,  S. ISAKSSON,  I. POSSERUD,* H. STRID,* H. SJO ¨ VALL* & M. SIMRE ´ N* *Institute of Medicine, The SahlgrenÕs Academy, University of Gothenburg, Sweden  Institute of Biomedicine, The SahlgrenÕs Academy, University of Gothenburg, Sweden Abstract Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probi- otic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifido- bacterium lactis B612. The phenotype of CD19 + B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells. Keywords immune activation, irritable bowel syndrome, lipopolysaccharide, lymphocyte, probiotics. INTRODUCTION Irritable bowel syndrome (IBS) may be the result of previous transient or chronic inflammation of the gut. 1–3 Increased activity of the innate and the adaptive immune response has during the last decade been suggested to be associated with IBS, but the explana- tion for the increased immune activity observed in IBS patients remains unclear. Recent studies have described the characteristics of the immune activity of IBS patients. Serum levels, and the degree of LPS triggered cell culture secretions of proinflammatory cytokines, seem to be enhanced in association with the development of IBS symptoms. 4,5 Additionally, increased presence of intestinal T cells has also been a frequently reported feature of IBS, although the mechanism for the expanded T-cell pool and/or the increased T-cell recruitment to the mucosa remains unknown. 6–11 So far, the properties of B cells of IBS patients have been relatively little studied. Several previous reports have however demonstrated increased serum levels of food specific IgG antibodies in IBS patients. 12–15 Antibody producing B cells play a central role in adaptive immune responses, as antibodies are impor- tant in defence against and clearance of infections. However, B cells also function as professional antigen presenting cells, expressing HLA-DR (MHC class II), and thus have the ability to present antigens to CD4 + T-helper cells. 16 In general, the ability of antigen presenting cells to induce T-cell activation is tightly linked to the maturation status of the presenting cell. B-cell activation and maturation largely depends on antigen recognition by the B-cell receptor (IgR). The Address for correspondence Lena O ¨ hman, Department of Microbiology and Immunology, University of Gothenburg, Box 435, 40530 Gothenburg, Sweden. Tel: +46 31 786 6214; fax: +46 31 786 6205; e-mail: lena.ohman@microbio.gu.se Received: 3 July 2008 Accepted for publication: 7 December 2008 Neurogastroenterol Motil (2009) 21, 644–e27 doi: 10.1111/j.1365-2982.2009.01272.x Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Publishing Ltd 644