The B cell-stimulating molecules, BAFF (B cell activating factor also known as BLyS; TALL-1; CD257 or TNFSF13B) and APRIL (a proliferation-inducing ligand, also known as CD256 or TNFSF13), are critical factors in the maintenance of the B cell pool and humoral immunity1,2.
APRIL is a secreted protein that binds to transmembrane activator and CAML interactor (TACI), B cell maturation antigen (BCMA) and heparan sulfate proteoglycans (HSPG). APRIL can interact with carbohydrate side chains of proteoglycans that may trigger cross-linking3.
BAFF is a transmembrane protein which is proteolytically processed by furin to be released as a soluble cytokine2. Soluble BAFF exists either as trimers (BAFF 3-mer), or as an ordered assembly of 20 trimers (BAFF 60-mer)4. BAFF 3-mer and BAFF 60-mer both signal through BAFF-R, only TACI (and BCMA) respond to BAFF 60-mer and not to BAFF 3-mer4. Similar observations are true with APRIL, which needs to be cross-linked in order to activate TACI4.
APRIL maintains B cell homeostasis by acting at a later stage, modulating the function and survival of antigen-experienced B cells. BAFF is a key survival factor for peripheral B cells and together with IL-6 responsible for plasma cell differentiation2. APRIL (as well as BAFF) stimulates class-switch recombination (CSR), hence contributes to shaping humoral effector mechanisms. With regards to humoral memory, APRIL is involved in the establishment and survival of the long-lived plasma cell (LLPC) pool in the bone marrow (BM)5. Besides its major role in B cell biology, BAFF co-stimulates activated T cells.
APRIL is expressed by a number of myeloid-derived cell types including BM granulocytes, megakaryocytes, eosinophils, osteoclasts, and by dendritic cells following exposure to IFN-α, IFN-γ or CD40L. APRIL expression is induced during hematopoiesis in the bone marrow. APRIL expression is not limited to cells of myeloid origin but can be found in epithelial cells of the gut, tonsil, breast and skin. Finally, APRIL is expressed in tumor cell lines and human cancer cells of colon, thyroid and lymphoid origin1.
BAFF is mainly produced by innate immune cells such as neutrophils, monocytes, macrophages, dendritic cells, follicular dendritic cells, T cells, activated B cells, some malignant B cells, but non-lymphoid cells like astrocytes, synoviocytes and epithelial cells can also produce BAFF.
BAFF and APRIL are implicated in several human autoimmune diseases with autoreactive B cell involvement, including systemic lupus erythematosus (SLE)6, Sjö gren’s syndrome (SS)7, IgA nephropathy (IgAN)8, and rheumatoid arthritis (RA)9. APRIL might also function in enhancing proliferation of some tumor cells, especially B cell malignancies10,11. BAFF levels are also increased in some lymphoid cancers12.
The APRIL (human) ELISA Kit (Item No. AG-45B-0012-KI01) is a sandwich ELISA for specific quantitative determination of human APRIL in serum, plasma and cell culture supernatants. This ELISA Kit shows both high specificity and high sensitivity, which is a clear advantage compared to other APRIL (human) ELISA Kits from key competitors.
The BAFF, Soluble (human) ELISA Kit (Item No. AG-45B-0001-KI01) is a sandwich ELISA for specific quantitative determination of human BAFF in serum, plasma and cell culture supernatants. This ELISA Kit does not cross-react with mouse BAFF and has been chosen by several CROs for its high specificity and high sensitivity