Integrin cd11b negatively regulates b cell receptor signaling to shape humoral response during immunization and autoimmunity

Mingqian Zhou, Paul Dascani, Chuanlin Ding, Justin T. Kos, David Tieri, Xiaoying Lin, Dawn Caster, David Powell, Chengping Wen, Corey T. Watson, Jun Yan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Our previous work has revealed the ability of CD11b to regulate BCR signaling and control autoimmune disease in mice. However, how CD11b regulates the immune response under normal conditions remains unknown. Through the use of a CD11b knockout model on a nonautoimmune background, we demonstrated that CD11b-deficient mice have an elevated Ag-specific humoral response on immunization. Deletion of CD11b resulted in elevated low-affinity and high-affinity IgG Ab and increases in Ag-specific germinal center B cells and plasma cells (PCs). Examination of BCR signaling in CD11b-deficient mice revealed defects in association of negative regulators pLyn and CD22 with the BCR, but increases in colocalizations between positive regulator pSyk and BCR after stimulation. Using a CD11b-reporter mouse model, we identified multiple novel CD11b-expressing B cell subsets that are dynamically altered during immunization. Subsequent experiments using a cell-specific CD11b deletion model revealed this effect to be B cell intrinsic and not altered by myeloid cell CD11b expression. Importantly, CD11b expression on PCs also impacts on BCR repertoire selection and diversity in autoimmunity. These studies describe a novel role for CD11b in regulation of the healthy humoral response and autoimmunity, and reveal previously unknown populations of CD11b-expressing B cell subsets, suggesting a complex function for CD11b in B cells during development and activation.

Original languageEnglish
Pages (from-to)1785-1797
Number of pages13
JournalJournal of Immunology
Volume207
Issue number7
DOIs
StatePublished - 1 Oct 2021
Externally publishedYes

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