CD27–CD70 selleck signals are important in the germinal differentiation of B cells into antibody-secreting plasma cells [14–16]. The importance of CD27–CD70 in autoimmune diseases has been underscored by a number of studies. CD27hi plasma B cells were shown to increase in humans afflicted with lupus and the increase was correlated with disease

severity [17]. That CD27hi B cells play critical roles in disease severity in patients with systemic lupus erythematosus (SLE) was confirmed by immunosuppressive therapy that resulted in a reduction of CD27hi plasma cells and concomitant disease remission [18]. In addition, soluble CD27 was found to be elevated in the sera of patients with SLE [19]. Furthermore, large numbers of human leucocyte antigen D-related (HLA-DR)hiCD27+ plasmablasts were found in patients with SLE, their numbers correlating with the extent of lupus activity and anti-dsDNA levels [20]. Similarly, CD70 was overexpressed in aged CD4+ T cells

in Pictilisib solubility dmso Murphy Roth Large (MRL)/lpr mice [21]. Treatment of Swiss Jackson Laboratory (SJL) mice with anti-CD70 antobodies was found to prevent the development of experimental autoimmune encephalomyelitis (EAE) in a TNF-α-dependent manner, but this effect was independent of impairment of T and B cell effector functions [22]. The mechanisms underlying these various effects are not clear. CD4+ T cells have been observed in synovia in rheumatoid arthritis, and psoriatic arthritis patients have been shown to express high levels of CD70 [23]. Treatment with anti-CD70 antibody led to significant improvement in clinical symptoms, and marked reductions

in autoantibody production, inflammation and bone and cartilage destruction [24] (Table 1, Fig. 1a). In chronic inflammatory disorders, B cells can contribute to tissue damage by producing autoantibodies and presenting antigens to T cells. B cells make important contributions to disease severity in autoimmune diseases such as rheumatoid arthritis (RA) Non-specific serine/threonine protein kinase [25]. Thus, CD27+ memory B cells were found to be very abundant in the synovial fluid of patients with juvenile idiopathic arthritis and are believed to prime T cells as a result of their increased expression of CD86 [26]. CD30 was identified originally in 1982 on tumour cells of Hodgkin’s lymphoma [27]. Also called Ki-1, it is a membrane glycoprotein consisting of two chains with molecular weights of 120 and 105 kDa. It is expressed by a subset of activated T cells (both CD4+ and CD8+), NK cells and B cells, and is expressed constitutively in decidual and exocrine pancreatic cells, with maximum expression on CD45RO+ memory T cells [28]. The CD30 ligand (CD30L; CD153) is a 26–40 kDa protein cloned in 1993 and present on a variety of cells, including activated T cells, macrophages, resting B cells, granulocytes, eosinophils and neutrophils [29].