Preprint Club
A cross-institutional Journal Club Initiative

Keywords

• Heart failure

• B cell

• Antigen presentation

Main Findings

Heart faillure is a leading cause of mortality. Acute ischemic myocardial injury leads to the activation of a robust infllammatory responses. While necessary to limit tissue injury and induce tissue repair, myocard inflammation has been shown to be accompaigned by infiltration of monocytes and B cells associated with adverse cardiac remodelling. This preprint by Lovell et al. evaluate the B-cell specific mechanisms contributing to adverse  remodelling within the cardio-splenic axis. Using adoptive transfer of splenic cells from a permanent coronary ligation model of isquemic heart faillure or controls intro naïve mice, the authors showed that B cells circulate to the recipient spleen and cardiac tissues to induce pathologic changes, measured by ventricular ejection fraction and ventricular end-systolic diameter. Transfered B cells from animals that underwent coronary ligation surgery also induced an increase of total splenic lymphocytes. Single-cell RNA transcriptomic anaylises revealed the upregulation of BCR mediated and antigen presentation pathways in splenic, peripheral blood and infiltrating cardiac B cells, following adoptive transfer and during acute ischemic heart faillure. The deletion of major histopatocombality complex MHC II on B cells (Cd19tm1(cre)Cgn/-H2-Ab1b-tm1Koni/ b-tm1Koni

Mice) prevented cardiac infiltration and remodelling. were not activation of these B cells confirming the central role of B-cell mediated antigen presentation in the adverse remodelling. Analyses of public transcriptmic data of B cells in human individuals with ischemic heart faillure confirm the dysregulation of antigen processind and resentation pathways.

Limitations

• It would be important to document the impact of surgery on MHC II KO mice on lymphocyte population. How these B cells compare to WT befroe adotive transfer?

• As adoptive transfer of CD4+ T cells from mice with ischemic heart faillure into naïve recipient has also been reported to induce adverse remodeling, it would be interesting to test whether CD4+ T cell depletion impacts on B-cell-mediated adverse cardiac remodeling observed.

• The use of either BCR or TCR transgenic recipient mice may help to undertand the role of various lymphocyte population.

Significance/Novelty

Accumulating evidence in pre-clinical but also clinical studies show the importance of B cells in adverse remodelling following ischemic heart faillure. Lovell et al. provide compelling evidence of the involvment of B-cell-mediated antigen presentation in ths process. Furthermore, their models offer an helpful plateform to understand the kinetics and cellular players involved in adverse remodelling.

Credit

Reviewed by Nicolas Ruffin as part of a cross-institutional journal club between the Icahn School of Medicine at Mount Sinai, the University of Oxford, the Karolinska Institute and the University of Toronto.

The author declares no conflict of interests in relation to their involvement in the review.