Flow Cytometric Characterization of Murine B Cell Development

Harris, Faith M.; Meagher, Karoline A; Zhong, Maggie; Daniel, Benjamin J.; Eckersdorff, Mark; Green, Jesse  A.; Voronina, Vera A.; Guo, Chunguang; Limnander, André; Macdonald, Lynn E.

doi:10.3791/61565

Cited by 3 publications

(1 citation statement)

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“…S13), which appeared relatively enriched in T1 cells due to cell loss at later stages (fig. S14) ( 65 , 66 ). LynA KO and LynB KO transitional cells generally had intermediate levels of MHCII expression, between WT and the significantly elevated levels in total Lyn KO cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

A dominant function of LynB kinase in preventing autoimmunity

et al. 2022

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Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynA KO ) or LynB KO mice. Autoimmune disease in total Lyn KO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete Lyn KO . Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).

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Section: Resultsmentioning

confidence: 99%

A dominant function of LynB kinase in preventing autoimmunity

et al. 2022

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Reduction of peritoneal cavity B1a cells in adult Slc7a5 knockdown mice via dysregulating the mTOR pathway

Sun

Wen

et al. 2023

International Immunopharmacology

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Maternal infection causes dysfunctional BCR signaling in male offspring due to aberrant Xist expression

Gibbs

Oviedo

Ondigo

et al. 2023

Preprint

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Infections during pregnancy with pathogens such as helminths correlate with altered immune responses to common childhood immunizations. However, the molecular mechanisms that underlie this remain unknown. Using our murine model of maternal schistosomiasis, when immunized, males from infected mothers had a lower frequency of antigen-specific germinal center B cells and downregulation of transcripts downstream of BCR signaling compared to males from uninfected mothers. This is driven by a reduction in developing B cell populations within the bone marrow of pups from infected mothers. Males from infected mothers were impacted to a greater extent than their female littermate counterparts. We found this defect to be caused by aberrant expression of the long non-coding RNA Xist in males leading to dysregulated Igalpha expression on developing B cells. This, for the first time, links dysfunctional BCR signaling with Xist expression, while also proposing a detrimental function for Xist expression in males.

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Flow Cytometric Characterization of Murine B Cell Development

Cited by 3 publications

References 0 publications

A dominant function of LynB kinase in preventing autoimmunity

A dominant function of LynB kinase in preventing autoimmunity

Reduction of peritoneal cavity B1a cells in adult Slc7a5 knockdown mice via dysregulating the mTOR pathway

Maternal infection causes dysfunctional BCR signaling in male offspring due to aberrant Xist expression

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