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Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype.

ABSTRACT: Although human B cells have been extensively studied, most reports have used peripheral blood as a source. Here, we used a unique tissue resource derived from healthy organ donors to deeply characterize human B-cell compartments across multiple tissues and donors. These datasets revealed that B cells in the blood are not in homeostasis with compartments in other tissues. We found striking donor-to-donor variability in the frequencies and isotype of CD27+ memory B cells (MBCs). A comprehensive antibody-based screen revealed markers of MBC and allowed identification of novel MBC subsets with distinct functions defined according to surface expression of CD69 and CD45RB. We defined a tissue-resident MBC phenotype that was predominant in the gut but absent in blood. RNA-sequencing of MBC subsets from multiple tissues revealed a tissue-resident MBC gene signature as well as gut- and spleen-specific signatures. Overall, these studies provide novel insights into the nature and function of human B-cell compartments across multiple tissues.

SUBMITTER: Weisel NM

PROVIDER: S-EPMC7731793 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:An animal's ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the ? lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several ? lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory.

Dataset Information

Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype.

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