Alt. symbols: APRIL | CD256

Approved name: TNF superfamily member 13
Alt. names: tumor necrosis factor (ligand) superfamily, member 13

Location: 17p13.1: 7558292 - 7561608 (+)
Gene type: protein_coding, 9 transcripts.

Scores: LoFtool: 0.200000 | pLI: 0.87776801 | LOEUF: 0.438

HGNC: 11928

NCBI: 8741, RefSeq: NG_029949.1

Ensembl: ENSG00000161955.17

LRG_ | Status: none

OMIM: 604472

Expression | ProteinAtlas

TNFSF13 encodes APRIL, which shares overlapping receptors and functions with BAFF, in addition to being able to form heterotrimers with it. APRIL secreted by BM eosinophils is thought to be important for the maintenance of Ig-secreting plasma cells (PMID: 21217761). Because of their partial functional redundancy and complex interactions, it has been difficult to deconvolute the specific roles played by BAFF and APRIL in the formation of mature B-cell populations.

Yeh et al. (2020) recently identified a homozygous TNFSF13 frameshift mutation that abolished mRNA and protein expression in an adult with diagnosis of CVID on the basis of mild infections and progressive hypogammaglobulinemia, but normal T- and B-cell levels and proliferative responses (PMID: 32298700). Patient cells also showed normal BCR repertoires, consistent with unperturbed SHM and CSR. In contrast to largely normal findings from prior animal data (PMID: 14988498, 14729948), the patient h ad low levels of all isotypes with significant MZ B cell expansion and markedly reduced peripheral blood plasmacytes. The authors hypothesized that the recirculating MZ memory B cells required continuous signaling from APRIL and other ligands to sustain lifelong antigen-independent, plasmacyte differentiation, maintenance, and baseline Ig production. Indeed, addition of recombinant APRIL to the patient's iPSC-monocyte-derived DC (moDC) co-culture with B cells rescued the latter’s impaired proliferation and plasmacyte differentiation. [Load More]