B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure

Area of Science:

• Immunology
• Cardiology
• Molecular Biology

Background:

• Cardiovascular disease is a leading global cause of death.
• Ischemic heart failure, following myocardial infarction, drives cardiac mortality.
• The spleen-heart axis, involving immune cell migration, exacerbates cardiac dysfunction.

Purpose of the Study:

• To elucidate the role of splenic immune cells in post-myocardial infarction heart failure.
• To investigate the specific mechanisms by which splenic B cells contribute to adverse cardiac remodeling.
• To identify novel therapeutic targets within the cardio-splenic axis.

Main Methods:

• Adoptive transfer of splenic B cells from heart failure mice to naive recipients.
• Single-cell RNA sequencing of splenic B cells.
• Utilizing transgenic mice with B cell-specific MHC II deletion.
• Analysis of circulating B cells from human myocardial infarction patients.

Main Results:

• Adoptive transfer of splenic B cells promoted adverse cardiac remodeling and inflammation.
• Single-cell RNA sequencing identified MHC II-mediated antigen presentation as a key B cell mechanism.
• B cell-specific MHC II deletion attenuated cardiac dysfunction.
• Human data corroborated the role of B cells and MHC II in myocardial infarction.

Conclusions:

• Splenic B cells, through MHC II-mediated antigen presentation, significantly contribute to heart failure progression.
• This study reveals a novel mechanism within the cardio-splenic axis.
• MHC II signaling in B cells represents a promising therapeutic target for chronic heart failure.