Antifibrotics Modify B-cell Induced Fibroblast Migration and Activation in IPF Patients

B-cell activation is increasingly linked to numerous fibrotic lung diseases and it is well-known that aggregates of lymphocytes form in the lung of many of these patients (1, 2). Activation of B-cells by pattern recognition receptors (PRR) drives the release of inflammatory cytokines, chemokines and metalloproteases important in the pathophysiology of pulmonary fibrosis (3-6). However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contribute to the inflammatory and pro-fibrotic milieu seen in IPF patients. B-cell stimulation by CpG and β-glucan via PRR resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell-mediated fibroblast activation are modifiable by antifibrotics but each seems to exert a specific and different effect. These results suggest that upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in IPF patients and antifibrotics are able to at least partially reverse these responses.