title: Germinal center B cells constitute a predominant physiological source of IL-4: implication for Th2 development in vivo.
abstract: Protective immunity depends upon the capability of the immune system to properly adapt the response to the nature of an infectious agent. CD4(+) Th cells are implicated in this orchestration by secreting a polarized pattern of cytokines. Although Th2 development in animal models and in human cells in vitro to a large extent depends on IL-4, the nature of the cells that provide the initial IL-4 in vivo is still elusive. In this report, we describe the anatomical localization as well as the identity of IL-4-producing cells in human tonsil, a representative secondary lymphoid organ. We demonstrate that IL-4 production is a normal and intrinsic feature of germinal center (GC) B cells. We also show that expression of IL-4 is highly confined to the GCs, in which the B cells constitute the prevalent cellular source. Furthermore, immunofluorescence analysis of colon mucosa reveals a strikingly similar pattern of IL-4-expressing cells compared with tonsils, demonstrating that IL-4 production from GC B cells is not a unique feature of the upper respiratory tract. Our results show that GCs provide the most appropriate microenvironment for IL-4-dependent Th2 polarization in vivo and imply a critical role for GC B cells in this differentiation process.
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Johansson-Lindbom
authors.forename: Carl A K
authors.initials: CA
authors.lastname: Borrebaeck
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4