B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles

Area of Science:

• Immunology
• Infectious Diseases
• Respiratory Medicine

Background:

• B cells are crucial for immunity but their function in the human lung during tuberculosis (TB) remains unclear.
• Previous research has not fully elucidated the specific B cell populations and their roles within the infected lung tissue.

Purpose of the Study:

• To characterize B cell populations in the lungs of patients with TB.
• To investigate the functional diversity and localization of B cells within TB-infected lung tissue.

Main Methods:

• Analysis of B cells from lung tissue and matched blood of TB patients.
• Utilized flow cytometry and transcriptomics to identify and profile B cell subsets.
• Examined antibody levels and reactivity in lung tissue.

Main Results:

• B cells were decreased in blood but increased in lung tissue, congregating in granuloma-associated lymphoid tissue.
• Identified diverse lung B cell populations including memory, germinal center, antibody-secreting, atypical proinflammatory, and regulatory subsets.
• Observed expanded B cell subsets in TB disease and high levels of Mycobacterium tuberculosis (Mtb)-reactive IgM antibodies that enhance phagocytosis.

Conclusions:

• The lungs of TB patients harbor functionally diverse B cell subsets.
• These subsets play localized roles in immunity and potentially immunopathology.
• Lung B cells and their associated antibodies represent potential targets for novel TB therapeutic interventions.