B Cell and Humoral Immunity in Mycobacterium Tuberculosis Infection

B cells and the antibodies they secrete are increasingly recognised as more than bystanders in the immune response to Mycobacterium tuberculosis (Mtb). Beyond antigen presentation and support for T cell activation, B cells can differentiate into plasma cells that produce specific immunoglobulins capable of neutralising key virulence factors, opsonising bacilli and engaging phagocytic cells via Fc receptors. Distinct B cell subsets, including tissue‐resident memory cells, germinal centre B cells and atypical populations, accumulate at sites of infection and contribute to localised granuloma formation. Humoral responses vary according to host factors such as age and sex and may correlate with progression from latent infection to active disease. Antibody isotype, epitope specificity and Fc‐mediated effector functions together determine the extent of protection or pathology. Harnessing this complexity holds promise for the development of novel diagnostics, therapeutic monoclonal antibodies and next‐generation vaccines that target both systemic and mucosal immunity.

Research from Nature Portfolio

Recent studies have demonstrated that demographic variables substantially influence humoral signatures associated with tuberculosis progression. Profiling of Mtb‐specific antibody repertoires in adolescents and adults revealed a composite SeroScore that predicts disease progression up to two years before clinical diagnosis, with stronger correlations observed in younger individuals and males. In parallel, single‐cell analyses of B cells from the lungs of patients with active disease have uncovered diverse functional subsets—including germinal centre, antibody‐secreting, regulatory and proinflammatory atypical B cells—organisation into granuloma‐associated lymphoid tissue and elevated local IgM levels that enhance phagocytosis of Mtb. Foundational work in nonhuman primates has further shown that intravenous BCG vaccination elicits robust IgM responses in both plasma and bronchoalveolar fluid, correlating with diminished bacterial burden and demonstrating direct antimicrobial activity of Mtb‐specific IgM monoclonal antibodies in vitro.

B Cell and Humoral Immunity in Mycobacterium Tuberculosis Infection publication trend

The graph below shows the total number of articles in b cell and humoral immunity in mycobacterium tuberculosis infection across all publications each year (not limited to Nature Index journals).

Technical terms

B cell: A lymphocyte responsible for generating antibodies and presenting antigen to T cells.

Humoral immunity: The branch of adaptive immunity mediated by antibodies secreted into body fluids.

Germinal centre: A specialised microenvironment in secondary lymphoid organs where B cells undergo maturation, somatic hypermutation and class switching.

Monoclonal antibody: A uniform immunoglobulin produced by a single B cell clone, specific for one epitope.

Fc receptor: A cell surface protein that binds the constant (Fc) region of antibodies to trigger effector mechanisms such as phagocytosis.

References

1. Age and sex influence antibody profiles associated with tuberculosis progression. Nature Microbiology (2024).
2. B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles. Communications Biology (2024).
3. Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques. Nature Immunology (2021).
4. An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis. npj Vaccines (2023).
5. Features and protective efficacy of human monoclonal antibodies targeting Mycobacterium tuberculosis arabinomannan. JCI Insight (2023).
6. Antibodies as clinical tools for tuberculosis. Frontiers in Immunology (2023).