Association between B Cell Growth Factors and Primary Sjögren’s Syndrome-Related Autoantibodies in Patients with Non-Hodgkin’s Lymphoma

Despite the overall success of using R-CHOP for the care for non-Hodgkin’s lymphoma patients, it is clear that the disease is quite complex and new insight is needed to further stratify the patient for a better personized treatment. In current study, based on previous studies from animal model, new panels combining well-established cytokine (BAFF) and autoantibodies (anti-SSA/Ro) with newly identified cytokine (IL14) and autoantibodies (TSA) were used to evaluate the association between B cell growth factor and Sjögren’s related autoantibodies in NHL patients. The result clearly indicates that there was a unique difference between BAFF and IL14 in association with autoantibodies. While serum BAFF was negatively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in GI lymphoma patient, IL14 was positively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in non-GI lymphoma patient. Long-term follow-ups on these patients and evaluation of their response to the R-CHOP treatment and recurrence rate will be very interesting. Our result provides a solid evidence to support using novel diagnostic panel to better stratify the NHL patients.

HRF-Interacting Molecules

Histamine-releasing factor (HRF), also termed translationally controlled tumor protein (TCTP) and fortilin, is a highly conserved, multi-functional protein. This protein within a cell plays a critical role in the fundamental processes of cell-cycle progression, proliferation, survival, and malignant transformation. The same protein, despite the lack of signal sequence, is secreted through a nonclassical secretory pathway. The secreted protein usually termed HRF can activate IgE-primed basophils and mast cells, and works as a B cell growth factor and a chemoattractant for eosinophils. This structurally well-characterized protein interacts with many proteins to perform its intracellular and extracellular functions. This review summarizes recent studies of HRF/TCTP-interacting proteins as a major driving force to decipher its functions.

The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells

Interleukin (IL) 6 is a proinflammtory cytokine produced by antigen-presenting cells and nonhematopoietic cells in response to external stimuli. It was initially identified as a B cell growth factor and inducer of plasma cell differentiation in vitro and plays an important role in antibody production and class switching in vivo. However, it is not clear whether IL-6 directly affects B cells or acts through other mechanisms. We show that IL-6 is sufficient and necessary to induce IL-21 production by naive and memory CD4+ T cells upon T cell receptor stimulation. IL-21 production by CD4+ T cells is required for IL-6 to promote B cell antibody production in vitro. Moreover, administration of IL-6 with inactive influenza virus enhances virus-specific antibody production, and importantly, this effect is dependent on IL-21. Thus, IL-6 promotes antibody production by promoting the B cell helper capabilities of CD4+ T cells through increased IL-21 production. IL-6 could therefore be a potential coadjuvant to enhance humoral immunity.