Functional characterization of CD11c+ age-associated B cells as memory B cells

Samuel W. Du, Tanvi Arkatkar, Fahd Al Qureshah, Holly M. Jacobs, Christopher D. Thouvenel, Kristy Chiang, Andrea D. Largent, Quan Zhen Li, Baidong Hou, David J. Rawlings, Shaun W. Jackson

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Age-associated B cells (ABCs) are a unique subset of B cells defined by surface CD11b and CD11c expression. Although ABC expansion has been observed in both human and animal studies in the setting of advanced age, during humoral autoimmunity and following viral infection, the functional properties of this cellular subset remain incompletely defined. In the current study, we demonstrate that ABCs fulfill the criteria for memory B cells (MBCs), based on evidence of Ag-dependent expansion and persistence in a state poised for rapid differentiation into Ab-secreting plasma cells during secondary responses. First, we show that a majority of ABCs are not actively cycling but exhibit an extensive replication history consistent with prior Ag engagement. Second, despite unswitched surface IgM expression, ABCs show evidence of activation-induced cytidine deaminase (AID)-dependent somatic hypermutation. Third, BCRs cloned from sorted ABCs exhibit broad autoreactivity and polyreactivity. Although the overall level of ABC self-reactivity was not increased relative to naive B cells, ABCs lacked features of functional anergy characteristic of autoreactive B cells. Fourth, ABCs express MBC surface markers consistent with being poised for rapid plasma cell differentiation during recall responses. Finally, in a murine model of viral infection, adoptively transferred CD11c+ B cells rapidly differentiated into class-switched Ab-secreting cells upon Ag rechallenge. In summary, we phenotypically and functionally characterize ABCs as IgM-expressing MBCs, findings that together implicate ABCs in the pathogenesis of systemic autoimmunity.

Original languageEnglish (US)
Pages (from-to)2817-2826
Number of pages10
JournalJournal of Immunology
Volume203
Issue number11
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Functional characterization of CD11c<sup>+</sup> age-associated B cells as memory B cells'. Together they form a unique fingerprint.

  • Cite this

    Du, S. W., Arkatkar, T., Al Qureshah, F., Jacobs, H. M., Thouvenel, C. D., Chiang, K., Largent, A. D., Li, Q. Z., Hou, B., Rawlings, D. J., & Jackson, S. W. (2019). Functional characterization of CD11c+ age-associated B cells as memory B cells. Journal of Immunology, 203(11), 2817-2826. https://doi.org/10.4049/jimmunol.1900404