Characterization of murine polyreactive antigen-binding B cells: presentation of antigens to T cells.
Monoclonal polyreactive antibodies (Ab) can bind, at low affinity, a variety of different self and non-self antigens (Ag). Recent studies in humans showed that polyreactive Ab are expressed on the surface of a subset of peripheral B lymphocytes and clonal analysis revealed that a variety of different Ag can bind to single cells expressing these Ab. To see if these polyreactive Ag-binding B (PAB) cells also are present in mice, fluorescein-conjugated Ag and FACS sorting were used to identify and separate PAB cells from non-polyreactive Ag-binding B cells. Depending on the Ag used for screening, up to one-third of mouse splenic B cells displayed polyreactive Ag-binding properties. Confirmation that the Ag actually bound to surface Ig came from treating PAB cells with anti-Ig which inhibited Ag binding by up to 80 %. Further studies showed that PAB cells could present Ag to Ag-specific T cells, but despite their Ag-presenting ability, PAB cells from normal mice failed to trigger Ag-specific T cells to proliferate. Analysis of the co-stimulatory molecules B7-1 and B7-2 showed that these molecules were not expressed on PAB cells from normal mice. These findings argue that the lack of co-stimulatory molecules on PAB cells is the most likely explanation for their failure to stimulate Ag-specific T cells. The ability of PAB cells from normal mice to bind and present Ag to Ag-specific T cells, without causing them to proliferate, suggests that PAB cells may contribute to the induction and / or maintenance of immunological tolerance.
Wang
Z
Z
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20892-4322, USA.
Chen
Z J
ZJ
Wheeler
J
J
Shen
S
S
Notkins
A L
AL
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006825:Hybridomas / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D010047:Ovalbumin