title: Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice.
abstract: OBJECTIVE
  NOD.Igmicro ( null ) mice lacking mature B cells are highly resistant to diabetes and display poor CD4 T cell responses to autoantigens. Nevertheless, the degree to which different B cell subsets contribute to diabetes in NOD mice remains unresolved. Due to their role in the recognition of microbial and autoantigens, peritoneal B cell characteristics were examined in NOD mice to see if they differ developmentally, phenotypically or functionally in aspects relevant to diabetogenesis.
  
  
  METHODS
  The population dynamics, activation state, migratory behaviour and antigen presentation function were investigated in NOD peritoneal B cells.
  
  
  RESULTS
  NOD peritoneal B cells were found to express abnormally high levels of co-stimulatory molecules (CD40, CD86 and CD69). In contrast, the expression of L-selectin and integrin alpha4beta1 was markedly reduced in NOD mice compared with BALB/c and C57BL/6 mice. The number of B cells in the peritoneum was lower in NOD than in control mice throughout development; migration of B cells from the peritoneum to the pancreatic lymph nodes in NOD mice was enhanced tenfold. NOD B cells showed no chemotactic response to sphingosine-1-phosphate, which normally acts to retain B cells in the peritoneum. Peritoneal B cells of NOD mice also presented insulin autoantigen to CD4 T cells, inducing T cell proliferation.
  
  
  CONCLUSIONS
  NOD peritoneal B cells are hyperactivated, migrate to the pancreatic lymph nodes and are capable of driving insulin-specific CD4 T cell activation. These characteristics could make them important for inducing or amplifying T cell responses against islet-antigens.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. catharina.alam@utu.fi
authors.forename: C
authors.initials: C
authors.lastname: Alam
authors.forename: S
authors.initials: S
authors.lastname: Valkonen
authors.forename: S
authors.initials: S
authors.lastname: Ohls
authors.forename: K
authors.initials: K
authors.lastname: Törnqvist
authors.forename: A
authors.initials: A
authors.lastname: Hänninen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001324:Autoantigens / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement; D015536:Down-Regulation; D005434:Flow Cytometry; D037181:Lectins, C-Type / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010179:Pancreas / Q000276:immunology / Q000502:physiology*; D010455:Peptides / Q000172:deficiency; D010529:Peritoneal Cavity / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012016:Reference Values; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D010455:Peptides; D000099192:CD69 Antigens; C010169:glucose utilization inhibitor