<p>Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease in which an impaired healing response to recurrent micro-injuries is thought to lead to fibrosis. Recent findings hint at a role for B cells and autoimmunity in IPF pathogenesis. We previously reported that circulating B cells from a fraction of patients, compared with healthy controls, express increased levels of the signaling molecule Bruton’s tyrosine kinase (BTK). However, it remains unclear whether B cell receptor (BCR) signaling is altered in IPF. Here, we show that the response to BCR stimulation is enhanced in peripheral blood B cells from treatment-naïve IPF patients. We observed increased anti-immunoglobulin-induced phosphorylation of BTK and its substrate phospholipase Cγ2 (PLCγ2) in naïve but not in memory B cells of patients with IPF. In naïve B cells of IPF patients enhanced BCR signaling correlated with surface expression of transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) but not B cell activating factor receptor (BAFFR), both of which provide pro-survival signals. Interestingly, treatment of IPF patients with nintedanib, a tyrosine kinase inhibitor with anti-fibrotic and anti-inflammatory activity, induced substantial changes in BCR signaling. These findings support the involvement of B cells in IPF pathogenesis and suggest that targeting BCR signaling has potential value as a treatment option.</p>

doi.org/10.3390/cells10061321, hdl.handle.net/1765/136944
Erasmus MC: University Medical Center Rotterdam

S.F.H. (Stefan) Neys, P. (Peter) Heukels, J.A.C. (Jennifer) van Hulst, J. (Jasper) Rip, Marlies S. Wijsenbeek, R.W. (Rudi) Hendriks, & O.B.J. (Odilia) Corneth. (2021). Aberrant B cell receptor signaling in naïve B cells from patients with idiopathic pulmonary fibrosis. Cells, 10(6). doi:10.3390/cells10061321