Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• B lymphocyte development involves V(D)J recombination and class switch recombination (CSR).
• Both processes require accessible DNA, facilitated by enzymes like recombination activating gene (RAG) and activation-induced cytidine deaminase (AID).
• Histone acetylation, particularly of H3K9 by GCN5 and PCAF, influences chromatin accessibility.

Purpose of the Study:

• To investigate the in vivo role of GCN5 and PCAF in B cell development.
• To determine the necessity of GCN5 and PCAF for V(D)J recombination and CSR.

Main Methods:

• Generation of a mouse model lacking both GCN5 and PCAF specifically in B cells.
• Analysis of B cell populations in bone marrow and peripheral lymphoid organs.
• Assessment of class switch recombination (CSR) levels.

Main Results:

• Double-deficient mice exhibited reduced mature B cell numbers in bone marrow and periphery.
• Accumulation of pro-B cells was observed in the bone marrow of double-deficient mice.
• Class switch recombination (CSR) levels were significantly reduced.

Conclusions:

• GCN5 and PCAF have redundant functions essential for B cell development.
• Both acetyltransferases are required for proper B lymphocyte maturation and CSR in vivo.