TACI Isoforms Regulate Ligand Binding and Receptor Function
Authors: Yolanda Garcia-Carmona
Jose Chavez
Charlotte Cunningham-Rundles
Lin Radigan
Eric Meffre
Andrea Cerutti
Adrian T Ting
Sai Krishna Athuluri Divakar
Journal: Frontiers in Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: B cell; TACI; TLR9; activation; isoforms.
Affiliations: Department of Clinical Immunology, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States., Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States., Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States., Catalan Institute for Research and Advance Studies (ICREA), Barcelona, Spain., Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions M√®diques (IMIM), Barcelona, Spain., Department of Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Abstract:  TACI signals activate B cell proliferation, isotype switch and antibody production in both normal immunity and autoimmune states. In contrast to murine TACI, the human TACI gene undergoes alternative splicing to produce short and long isoforms (TACI-S and TACI-L). In previous studies, we showed that transduction of the short, but not long isoform, into murine B cells or human pre-B cells lacking TACI, caused them to become transcriptional and morphologically identical to plasma cells. These data suggest that the expression of different isoforms in humans provides unique controls on B cell maturation. In these studies we show that TACI-S and TACI-L form complexes in a ligand-independent manner, not dependent on a single extracellular domain. Both TACI isoforms are detectable in the endosomal cellular compartment where they co-localize with MyD88, TRAF6, and the activated 65 kDa form of TLR9, depending on a conserved intracellular TACI sequence. In contrast to TACI-L expressing cells, or cells bearing both isoforms, TACI-S binds ligands BAFF and APRIL with substantially greater affinity and promotes enhanced NF-kB activation. Using isoform-specific monoclonal antibodies, we show that while TACI-L is predominant as a surface receptor surface on human B cells, significantly more TACI-S is noted in the intracellular compartment and also in marginal zone, isotype switched and plasmablast in resting B cells. TACI-S is increased in tonsillar B cells and also in the intracellular compartment of activated peripheral B cells. These data shows that alternative splicing of the human TACI gene leads to two isoforms both of which intersect with MyD88 and TRAF6 and form complexes with TLR9, but the two isoforms have different ligand binding capacities, subcellular locations and activation capabilities. 

Retracted: No

PubPeer comments:
 1. Fig. 1 of this paper is highly similar to the Fig. 1 of paper Physica B 407 (2012) 3774u20133780:   2. The area of Fig. 2d of this paper, which is indicated by the RED box, is highly similar to Fig. 2b of paper Physica B 407 (2012) 3774u20133780:   3. Figs. 3 and 4 of this paper are highly similar to Figs. 3 and 4 of paper Physica B 407 (2012) 3774u20133780:   Could the authors please give explanations to these similarities ? , 
 Dear Horornis Flavolivaceus, Thank you for bring this to my attention. I agree with you that XRD pattern, SEM figure of x = 0.18, M (T) and M (H) at T = 300 K is identical because of measurement result from same composites with formula of (1-x) La0.7Sr0.3MnO3 xBaTiO3. If measured results physical quantities in the same samples to give differ that proves the results are not repeatable, and therefore the scientific meanings be can t accept. Our team includes PT Phong, TD Thanh, NV Dang, NV Khien, DH Manh, TL Phan under the guidance of Professor Le Van Hong and collaborating with Professor In-Ja Lee (Dongguk University) and Professor SC Yu (Chungbuk National University) fabricated the (1-x) La0.7Sr0.3MnO3 xBaTiO3 composites, then we measured and assigned the member of team write the manuscript. The first draft focused on the explanation the conductivity characteristics of composites using different models and provided evidence that when BaTiO3 was present at the grain boundaries, both LFMR and HFMR increased. This manuscript has been accepted for publication in the Physica B The second draft mainly studies the effect of BaTiO3 on LFMR enhancement of (1-x) La0.7Sr0.3MnO3 xBaTiO3 using the phenomenological model of Raychaudhuri et al. to analyze the LFMR component from MR (T) for 4 samples (x = 0, x = 0.06, x = 0.12 and x = 0.18). This manuscript has been accepted in the journal J Mater Sci: Mater Electron. Both above contents from 2 articles of our team need to solve a common problem that is to prove that BaTiO3 exists only at the grain boundary without participating in the perovskite structure of La0.7Sr0.3MnO3. To do that, we have to use all four different experiments simultaneously, that is to determine the structure through XRD, the morphology of particles through SEM, Curie temperature through M (T) and decreasing of Ms through M (H). For this reason, we used XRD, SEM, M (T) and M (H) in both above articles of our group, as you have seen. Once again, I thank you very much for careful reading our articles. Sincerely, ,