title: Divergent transcriptional programming of class-specific B cell memory by T-bet and RORα.
abstract: Antibody class defines function in B cell immunity, but how class is propagated into B cell memory remains poorly understood. Here we demonstrate that memory B cell subsets unexpectedly diverged across antibody class through differences in the effects of major transcriptional regulators. Conditional genetic deletion of the gene encoding the transcription factor T-bet selectively blocked the formation and antigen-specific response of memory B cells expressing immunoglobulin G2a (IgG2a) in vivo. Cell-intrinsic expression of T-bet regulated expression of the transcription factor STAT1, steady-state cell survival and transcription of IgG2a-containing B cell antigen receptors (BCRs). In contrast, the transcription factor RORα and not T-bet was expressed in IgA(+) memory B cells, with evidence that knockdown of RORα mRNA expression and chemical inhibition of transcriptional activity also resulted in lower survival and BCR expression of IgA(+) memory B cells. Thus, divergent transcriptional regulators dynamically maintain subset integrity to promote specialized immune function in class-specific memory B cells.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Wang
authors.forename: Louise J
authors.initials: LJ
authors.lastname: McHeyzer-Williams
authors.forename: Shinji L
authors.initials: SL
authors.lastname: Okitsu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Burris
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
authors.forename: Michael G
authors.initials: MG
authors.lastname: McHeyzer-Williams
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D057050:Receptor Tyrosine Kinase-like Orphan Receptors