| Autor: |
Chiang, Kristy, Largent, Andrea D., Arkatkar, Tanvi, Thouvenel, Christopher D., Du, Samuel W., Shumlak, Natali, Woods, Jonathan, Li, Quan-Zhen, Liu, Yifan, Hou, Baidong, Rawlings, David J., Jackson, Shaun W. |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
J Immunol |
| Popis: |
Cognate interactions between autoreactive B and T cells promote systemic lupus erythematosus (SLE) pathogenesis by, inter alia, facilitating spontaneous germinal center (GC) formation. Whereas both myeloid and B cell antigen presenting cells (APCs) express B7 ligands (CD80 and CD86), the prevailing model holds that dendritic cell (DC) costimulation is sufficient for CD28-dependent T cell activation. Here, we report that B cell-intrinsic CD80/CD86 deletion unexpectedly abrogates GCs in murine lupus. Interestingly, absent GCs differentially impacted serum autoantibodies (autoAb). In keeping with distinct extra-follicular (EF) and GC activation pathways driving lupus autoAb, lack of GCs correlated with loss of RNA-associated autoAb but preserved anti-dsDNA and connective tissue autoAb titers. Strikingly, even heterozygous B cell CD80/CD86 deletion was sufficient to prevent autoimmune GCs and RNA-associated autoAb. Together, these findings identify a key mechanism whereby B cells promote lupus pathogenesis, by providing a threshold of costimulatory signals required for autoreactive T cell activation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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