title: Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma RII-mediated B cell suppression.
abstract: Inhibitory receptors CD22, Fc gamma RII (CD32), CD72, and paired immunoglobulin-like receptor (PIR)-B are critically involved in negatively regulating the B cell immune response and in preventing autoimmunity. Here we show that interleukin 4 (IL-4) reduces expression of all four on activated B cells at the level of messenger RNA and protein. This reduced expression is dependent on continuous exposure to IL-4 and is mediated through Stat6. Coligation of Fc gamma RII to the B cell receptor (BCR) via intact IgG increases the B cell activation threshold and suppresses antigen presentation. IL-4 completely abolishes these negative regulatory effects of Fc gamma RII. CD22 coligation with the BCR also suppresses activation -- this suppression too is abolished by IL-4. Thus, IL-4 is likely to enhance the B cell immune response by releasing B cells from inhibitory receptor suppression. By this coordinate reduction in expression of inhibitory receptors, and release from CD22 and Fc gamma RII-mediated inhibition, IL-4 is likely to play a role in T cell help of B cells and the development of T helper cell type 2 responses. Conversely, B cell activation in the absence of IL-4 would be more difficult to achieve, contributing to the maintenance of B cell tolerance in the absence of T cell help.
authors.affiliation: Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom.
authors.forename: Elizabeth U
authors.initials: EU
authors.lastname: Rudge
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Pritchard
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002118:Calcium; D015815:Cell Adhesion Molecules; D015870:Gene Expression; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology; D037102:Lectins; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000235:genetics; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D050800:STAT6 Transcription Factor; D051918:Sialic Acid Binding Ig-like Lectin 2; D015534:Trans-Activators / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C064228:CD72 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; C105949:Pirb protein, mouse; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D002118:Calcium