CD4 T cells endow memory B cells with unique functional properties and transcriptional programming through direct interactions

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B707
Abstract ID: 5304

Presenting Author:
Christopher D. Scharer , Associate Professor at Emory Univ. Sch. of Med.

Abstract:

Memory B cells (MBC) exhibit enhanced functional properties compared to antigen-inexperienced naïve B cells, including class-switched, affinity matured B cell receptors (BCR) and can become resident in tissues.  Although MBC can form in a T cell independent manner, without transiting through a germinal center (GC), many of the enhanced properties require CD4 T cells and only arise from GC-dependent MBC lineages.  Currently it is not known what the full spectrum of molecular properties that are imparted to MBC through interactions with CD4 T cells.  To address this, MHCII-deficient (KO) mice, which lack CD4 T cells, were intranasally infected with influenza and the MBC that formed phenotyped.  Additionally, to further determine if direct interactions with CD4 T cells were important, WT and KO B cells were co-transferred into a WT host and the resulting cell fates determined.  Compared to WT B cells, KO B cells formed IgM+ MBC, but significantly reduced frequencies of class-switched MBC and plasma cells.  Consistent with previous data, no KO B cells displayed GC phenotypes, indicating the IgM MBC that did form differentiated in the extrafollicular space.  Using scRNA-seq we further defined the gene expression signatures in WT and KO MBC.  These data indicate that direct interactions with CD4 T cells are critical to initiate a transcriptional program that enhances survival and licenses MBC to migrate and establish residency in the lung following an intranasal viral infection.