B cell MHC haplotype affects follicular inclusion, germinal center participation and plasma cell differentiation in a mouse model of lupus

MHC class II molecules are essential for appropriate immune responses against pathogens but are also implicated in pathological responses in autoimmune diseases and transplant rejection. Previous studies have shed light on the systemic contributions of MHC haplotypes to the development and severity...

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Bibliographic Details
Published in:Frontiers in immunology 2023-11, Vol.14, p.1258046-1258046
Main Authors: Wibrand, Camilla, Wittenborn, Thomas R, Voss, Lasse Frank, Winther, Gudrun, Jensen, Lisbeth, Ferapontov, Alexey, Fonager, Sofie V, Fahlquist-Hagert, Cecilia, Degn, Søren E
Format: Article
Language:English
Subjects:
Animals
autoantibodies
Autoimmune Diseases
autoimmunity
B cells
Cell Differentiation
complement
Germinal Center
germinal centers
Haplotypes
Immunology
Lupus Erythematosus, Systemic - genetics
MHC
Mice
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Summary:MHC class II molecules are essential for appropriate immune responses against pathogens but are also implicated in pathological responses in autoimmune diseases and transplant rejection. Previous studies have shed light on the systemic contributions of MHC haplotypes to the development and severity of autoimmune diseases. In this study, we addressed the B cell intrinsic MHC haplotype impact on follicular inclusion, germinal center (GC) participation and plasma cell (PC) differentiation in the context of systemic lupus erythematosus (SLE). We leveraged the 564Igi mouse model which harbors a B cell receptor knock-in from an autoreactive B cell clone recognizing ribonuclear components, including double-stranded DNA (dsDNA). This model recapitulates the central hallmarks of the early stages of SLE. We compared 564Igi heterozygous offspring on either H2b/b, H2b/d, or H2d/d background. This revealed significantly higher germinal center (GC) B cell levels in the spleens of H2b/b and H2b/d as compared to H2d/d (p
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1258046