title: Incomplete activation of CD4 T cells by antigen-presenting transitional immature B cells: implications for peripheral B and T cell responsiveness.
abstract: B cells leave the bone marrow as transitional B cells. Transitional B cells represent a target of negative selection and peripheral tolerance, both of which are abrogated in vitro by mediators of T cell help. In vitro, transitional and mature B cells differ in their responses to B cell receptor ligation. Whereas mature B cells up-regulate the T cell costimulatory molecule CD86 (B7.2) and are activated, transitional B cells do not and undergo apoptosis. The ability of transitional B cells to process and present Ag to CD4 T cells and to elicit protective signals in the absence of CD86 up-regulation was investigated. We report that transitional B cells can process and present Ag as peptide:MHC class II complexes. However, their ability to activate T cells and elicit help signals from CD4-expressing Th cells was compromised compared with mature B cells, unless exogenous T cell costimulation was provided. A stringent requirement for CD28 costimulation was not evident in interactions between transitional B cells and preactivated CD4-expressing T cells, indicating that T cells involved in vivo in an ongoing immune response might rescue Ag-specific transitional B cells from negative selection. These data suggest that during an immune response, immature B cells may be able to sustain the responses of preactivated CD4(+) T cells, while being unable to initiate activation of naive T cells. Furthermore, the ability of preactivated, but not naive T cells to provide survival signals to B cell receptor-engaged transitional immature B cells argues that these B cells may be directed toward activation rather than negative selection when encountering Ag in the context of a pre-existing immune response.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Chung
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wells
authors.forename: Scott
authors.initials: S
authors.lastname: Adler
authors.forename: Anand
authors.initials: A
authors.lastname: Jacob
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: John G
authors.initials: JG
authors.lastname: Monroe
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D024201:Bystander Effect / Q000276:immunology*; D018106:CD28 Antigens / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy; D018920:Coculture Techniques; D004705:Endocytosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; C111390:OVA 323-339; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell; D010047:Ovalbumin