B lymphocytes on the front line of autoimmunity Pierre Youinou * , Sophie Hillion, Christophe Jamin, Jacques-Olivier Pers, Alain Saraux, Yves Renaudineau Laboratory of Immunology, Brest University Medical School Hospital, BP824, F29609 Brest Cedex, France Received 30 March 2005; accepted 6 June 2005 Available online 16 August 2005 Abstract The paradigm that B cell response to self antigens (Ag) is promoted by antibodies (Ab) has become unsatisfactory. Studies over the last decade have indeed revealed that B cells serve extraordinarily diverse functions within the immune system other than Ab production. They normally play a role in the development in the regulation, as well as the activation of lymphoid architecture, regulating dentritic cells and T cell subsets function through cytokine production. Receptor editing is also essential in B cells and aids in preventing autoimmunity. Both abnormalities in the distribution of B cells subsets and clinical benefit response to B cell depletion in autoimmune states illustrate their importance. Transgenic animal models have demonstrated that sensitivity of B cells to Ag receptor cross-linking correlates to autoimmunity: negative signaling by CD5 and CD22 in maintaining tolerance through recruitment of phosphatase has thus been documented. In short, a new area has been reached, whereby B lymphocytes return as a significant contributor to autoimmune disorders. D 2005 Elsevier B.V. All rights reserved. Keywords: B lymphocyte; Autoimmune disease; Dendritic cell; T lymphocyte; B cell antigen receptor; CD5 Contents 1. Subpopulations of B lymphocytes ........................................ 216 1.1. Classification according to the expression of CD5 ............................ 216 1.2. B lymphocyte ontogenesis ......................................... 217 1.3. Maturation of B cells in the germinal centers ............................... 217 2. Various functions of B cells ........................................... 217 2.1. Influence of B lymphocytes on neighboring cells ............................. 217 2.2. B lymphocytes as antigen-presenting cells................................. 218 2.3. Polarized cytokine production by B cells ................................. 218 1568-9972/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2005.06.011 * Corresponding author. Tel.: +33 298 22 33 84; fax: +33 298 22 38 47. E-mail address: youinou@univ-brest.fr (P. Youinou). Autoimmunity Reviews 5 (2006) 215 – 221 www.elsevier.com/locate/autrev