Cutting edge: Bcl6-interacting corepressor contributes to germinal center T follicular helper cell formation and B...

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• T follicular helper (Tfh) cells are essential for adaptive immunity, supporting B cell maturation into antibody-producing plasma cells and memory cells.
• The transcriptional repressor Bcl6 is a key regulator of Tfh cell development within germinal centers (GCs).
• BCOR, a component of Polycomb repressive complexes, interacts with Bcl6 and may influence Tfh differentiation.

Purpose of the Study:

• To investigate the role of BCOR in T cell-expressed genes during GC-Tfh cell differentiation.
• To determine the impact of BCOR deficiency on GC-Tfh cell formation and function in vivo.

Main Methods:

• Utilizing a mouse model with T cell-specific deletion of BCOR.
• Infecting mice with Listeria monocytogenes and immunizing with peptide in CFA to induce GC-Tfh responses.
• Quantifying GC-Tfh cells, plasma cells, and GC B cells via flow cytometry and immunological assays.

Main Results:

• T cell-targeted BCOR deficiency resulted in a significant reduction of peptide:MHC class II-specific GC-Tfh cells after Listeria monocytogenes infection.
• A 2-fold decrease in GC-Tfh cells was observed following immunization with a peptide in CFA in BCOR-deficient mice.
• Diminished plasma cell and germinal center B cell formation was associated with the loss of GC-Tfh cells.

Conclusions:

• T cell-expressed BCOR is critical for the optimal differentiation and maintenance of GC-Tfh cells.
• BCOR plays a vital role in supporting robust humoral immunity by regulating GC-Tfh cell development.
• These findings highlight BCOR as a key molecular player in Tfh cell biology and immune responses.