ZBTB32 Restricts the Duration of Memory B Cell Recall Responses

J Immunol. 2016 Aug 15;197(4):1159-68. doi: 10.4049/jimmunol.1600882. Epub 2016 Jun 29.

Abstract

Memory B cell responses are more rapid and of greater magnitude than are primary Ab responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of Ab recall responses. ZBTB32 is highly expressed by mouse and human memory B cells but not by their naive counterparts. Zbtb32(-/-) mice mount normal primary Ab responses to T-dependent Ags. However, Zbtb32(-/-) memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32(-/-) secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32(-/-) secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of Ab recall responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Humans
  • Immunologic Memory / immunology*
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Polymerase Chain Reaction
  • Repressor Proteins / immunology*

Substances

  • Repressor Proteins
  • Rog protein, mouse
  • TZFP protein, human