Expansion of marginal zone B cells is not sufficient for the development of renal disease in NZBxNZW F1 mice.
The mechanisms which govern the production of autoantibodies and of tissue damage during systemic lupus (SLE) are still unclear. In the NZBxNZW F1 (BW) model of SLE glomerulonephritis, the activation and commitment of B cells are thought to play a major role in disease progression. Previous analysis has suggested that these mice have a substantial increase of marginal zone (MZ) B cells before the occurrence of the disease. Owing to the probable role of this B cell subset in autoantibody production, it was important to define the possible link between this abnormality and the occurrence of kidney damage. Using cytofluorometry analysis, we followed the splenic MZ B cell phenotype in different series of mice with shared autoimmune genetic background and histologically defined renal status. By comparing BW females and BW males, NZB and NZW mice, we confirm that BW mice have an increase in MZ B cells but this MZ B cells expansion is not directly linked to tissue lesions. Genetically modified BW female mice with a restricted repertoire of B and T cell antigen receptors, and which do not develop nephritis, exhibit the same increase of MZ B cells, suggesting that this increase does not depend on a specific set of antigens. Moreover, our analysis brings to light a pre-disease state in BW males, with autoantibody production and mesangial deposits.
Schuster
H
H
Laboratoire d'Immunopathologie, Institut d'Hématologie et d'Immunologie, Strasbourg, France.
Martin
T
T
Marcellin
L
L
Garaud
J C
JC
Pasquali
J L
JL
Korganow
A S
AS
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000502:physiology*; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D001323:Autoantibodies; D011947:Receptors, Antigen, B-Cell