B Cell Survival in Intragraft Tertiary Lymphoid Organs After Rituximab Therapy

Abstract

In certain patients, inflammatory microenvironment provides BAFF-dependent paracrine survival signal to B-cells in TLOs, allowing them to escape rituximab-induced apoptosis, thereby thwarting therapeutic efficiency.

Intragraft Th17 Infiltrate Promotes Lymphoid Neogenesis and Hastens Clinical Chronic Rejection

“…Our group (18,21,23) and others (17,41) have contributed to document the role of lymphoid neogenesis, namely, the progressive organization of inflammatory cells into structures that morphologically resemble secondary lymphoid organs (42) during chronic rejection. Accumulating evidence indeed suggests that intragraft ectopic germinal centers support the maturation of a local humoral immune response, which in turn contributes to tissue destruction (21)(22)(23). The close correlation observed between the levels of expression of AID (the key enzyme in the germinal center reaction) and IL-21 leads us to propose that Th17 cells hasten graft destruction by promoting lymphoid neogenesis through the production of IL-21.…”

“…Several studies have indeed reported that intragraft ectopic germinal centers are the site of elicitation of a local humoral immune response (18,(21)(22)(23).…”

Immune infiltration in human tumors: a prognostic factor that should not be ignored

“…Tertiary lymphoid structures have been detected in peripheral lymphoid organs in a variety of autoimmune diseases and in graft rejection (Thaunat et al, 2008). In this situation, their increase in size and number correlates with disease severity and local production of autoantibodies with an oligoclonal repertoire and hypersomatic mutations (Gause et al, 1995;Kotlan et al, 2003;RangelMoreno et al, 2006;Carragher et al, 2008;Humby et al, 2009).…”

Once Upon a Time: The Adaptive Immune Response in Atherosclerosis—a Fairy Tale No More

“…The existence of this lymphoid neogenesis in the aorta might impair the efficiency of therapeutic strategies targeting the immune system, such as B2 cell depletion, as it occurs in other chronic inflammatory settings such as chronic graft rejection. For instance, rituximab (anti-CD20 antibody) treatment, which depletes circulating B cells, failed to eliminate the intragraft B cells in the context of renal allograft (where TLOs develop in the interstitium of the graft) and local alloantibody production persisted (34). This might be due to the enrichment in B-cell survival factors within the graft inflammatory microenvironment.…”

“…Interestingly, in line with the proatherogenic role of B2 cells, it has been suggested that rituximab (anti-CD20) can become a treatment in atherosclerosis (19,20). However, it would be important to verify that this treatment also depletes B cells from TLOs during atherosclerosis, considering that this is not the case in the context of allograft (34), and that aortic TLOs are sites of B-cell activation (29). Another strategy to impair B2 cell function would be to block their activation by Tfh cells.…”