title: Subset size, activation threshold and distribution of autoreactive MZ and FO B cells do not differ in a sex-specific manner in the NZB/W F1 murine lupus model: an experimental mouse study.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) shows a strong sex bias, preferentially affecting females, and B cells are thought to play a pivotal role in its pathogenesis. Here, we compared the splenic B-cell compartments, their autoreactivity and activation threshold of female and male NZB/W F1, a murine lupus model reflecting the sex bias observed in patients with SLE.
  
  
  METHODS
  Autoantibody levels and the amount of autoantibody secreting cells were determined using ELISA and ELISPOT. Flow cytometry and immunofluorescence were applied to analyse the composition of the splenic B-cell pool. Purified follicular (FO) and marginal zone (MZ) B cells were stimulated and the frequency of autoreactive cells was determined. Finally, the proliferative response of FO and MZ B cells upon stimulation was assessed using CFSE dilution and [(3)H]-Thymidin incorporation.
  
  
  RESULTS
  Higher autoantibody titres were detected in female NZB/W F1 mice, which were mainly produced in the spleen. Analysing the composition of the splenic B-cell subsets, no differences were found prior to disease development. Autoreactive dsDNA-specific B cells were mostly found in the MZ compartment, while SmD1((83-119))-reactive cells were more evenly distributed. Equal frequencies of autoreactive B cells were found in female and malemice, and no difference in the response to polyclonal stimuli of the cells of both sexes was detected.
  
  
  CONCLUSIONS
  No differences in the composition or functionality of splenic B cells were observed that account for the different disease course in both sexes.
authors.affiliation: Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. philipp.enghard@charite.de
authors.forename: P
authors.initials: P
authors.lastname: Enghard
authors.forename: E
authors.initials: E
authors.lastname: Grussie
authors.forename: C
authors.initials: C
authors.lastname: Rieder
authors.forename: G-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: G
authors.initials: G
authors.lastname: Riemekasten
mesh_terms: D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D010446:Peptide Fragments / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D012727:Sex Characteristics; D013154:Spleen / Q000276:immunology / Q000473:pathology; D055517:snRNP Core Proteins
chemical_list: D000974:Antibodies, Antinuclear; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; C489793:Snrpd1 protein, mouse; D055517:snRNP Core Proteins