Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response

Area of Science:

• Immunology
• Molecular Biology
• Gene Regulation

Background:

• The germinal center (GC) response is vital for generating high-affinity antibodies during T cell-dependent (TD) immune responses.
• Posttranscriptional gene regulation, including minor intron splicing, plays a key role in controlling this process.
• RNPC3 (RNA-binding region containing 3) is essential for minor intron splicing by stabilizing the U11/U12 di-snRNP complex.

Purpose of the Study:

• To investigate the role of RNPC3 and its associated gene regulatory mechanisms in the TD immune response.
• To determine the impact of RNPC3 deficiency on GC B cell function and antibody generation.

Main Methods:

• Conditional ablation of RNPC3 in activated B cells in mice.
• Analysis of GC B cell proliferation and apoptosis.
• Investigation of minor intron removal from target genes using a minor spliceosome-dependent mechanism.

Main Results:

• Mice with RNPC3-deficient B cells exhibited defective antibody generation due to an impaired GC B cell response.
• RNPC3 deficiency inhibited the proliferation and promoted the apoptosis of activated B cells.
• RNPC3 regulates GC B cell development by controlling minor intron removal in genes involved in cell proliferation and apoptosis.

Conclusions:

• RNPC3 plays a critical, previously unrecognized role in regulating GC B cell responses.
• RNPC3-dependent minor intron splicing is essential for proper B cell function and antibody production during TD immune responses.