Abstract
Class switch recombination imparts B cells with a fitness-associated adaptive advantage during a humoral immune response by using a precision-tailored DNA excision and ligation process to swap the default constant region gene of the antibody with a new one that has unique effector functions. This secondary diversification of the antibody repertoire is a hallmark of the adaptability of B cells when confronted with environmental and pathogenic challenges. Given that the nucleotide sequence of genes during class switching remains unchanged (genetic constraints), it is logical and necessary therefore, to integrate the adaptability of B cells to an epigenetic state, which is dynamic and can be heritably modulated before, after, or even during an antibody-dependent immune response. Epigenetic regulation encompasses heritable changes that affect function (phenotype) without altering the sequence information embedded in a gene, and include histone, DNA and RNA modifications. Here, we review current literature on how B cells use an epigenetic code language as a means to ensure antibody plasticity in light of pathogenic insults.
Highlights
Genes are the basic molecular unit of heredity in all organisms since it is the gene and not the trait that is inherited
The function of mixed-lineage leukemia (MLL)-like H3K4 methyl transferase complex in Class switch recombination (CSR) was tested by deletion of a key component PTIP conditionally in B cells [24, 25]
These studies revealed that compromised H3K4me and acetylation and global chromatin architectural changes associated with the loss of PTIP leads to decreased S region accessibility, germline transcription, and compromised CSR to multiple isotypes [24, 25]
Summary
Genes are the basic molecular unit of heredity in all organisms since it is the gene (genotype) and not the trait (phenotype; except for imprinted genes) that is inherited. Epigenetic regulation includes non-coding RNAs (micro-RNA and long non-coding RNA), which can directly or indirectly (via recruitment of proteins) affect gene expression [4,5,6]. Histone modifications like H3K4me and H3K9ac are present at Sμ in naïve B cells and increases upon stimulation [16,17,18,19] These are marks associated with an open chromatin conformation that would favor accessibility of the CSR machinery including tethering AID to donor S region. Knockdown of histone chaperone FACT complex components (SSRP1 and SPT16), Spt, and methyl transferases (Ash and Wdr5) in CH12F3 cells have revealed the pertinence of the histone marks in regulating locus accessibility and S region cleavage, and CSR to IgA, a function which extends beyond germline transcript induction [20,21,22]. Scheme for CSR to IgE is shown; block curved arrows indicate germline transcription from promoters upstream of Sμ and Sε; *represents a putative, but uncharacterized switch region upstream of Cδ
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
