CD38 is a 42-kilodalton glycoprotein expressed extensively on B and T lymphocytes. CD38 exhibits a structural homology to Aplysia adenosine diphosphate (ADP)-ribosyl cyclase. This enzyme catalyzes the synthesis of cyclic ADP-ribose (cADPR), a metabolite of nicotinamide adenine dinucleotide (NAD ⁺ ) with calcium-mobilizing activity. A complementary DNA encoding the extracellular domain of murine CD38 was constructed and expressed, and the resultant recombinant soluble CD38 was purified to homogeneity. Soluble CD38 catalyzed the formation and hydrolysis of cADPR when added to NAD ⁺ . Purified cADPR augmented the proliferative response of activated murine B cells, potentially implicating the enzymatic activity of CD38 in lymphocyte function.

CD38 is an ∼45-kDa type II transmembrane glycoprotein expressed by hematopoietic and nonhematopoietic cells. Its surface expression is under complex control and varies during lymphocyte development, activation, and differentiation, suggesting an important role in these processes. Murine CD38 has been mainly characterized on B lymphocytes, and in humans, the molecule has been studied in T cells. This paper provides evidences that murine CD38 is regulated tightly during T cell activation and differentiation. On the periphery, a subset of mature T lymphocytes was identified by the expression of CD38. These cells showed an activated phenotype; they were larger and more granular than their negative counterparts. In accord with this observation, in vitro-activated T cells up-regulated CD38. Memory T lymphocytes also were CD38-positive. It is interesting that T cells expressing high levels of CD38 had a reduced, proliferative capacity but displayed an improved potential to produce interleukin-2 and interferon-γ, suggesting a role of this molecule during T cell activation and differentiation.

Btk is the protein affected in XLA, a disease identified as a B cell differentiation defect. Btk is crucial for B cell differentiation and activation, but its role in other cells is not fully understood. This review focuses on the function of Btk in monocytes, neutrophils, and platelets and the receptors and signaling cascades in such cells with which Btk is associated.

IL‐12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL‐12Rβ1 is a receptor chain of both the IL‐12 and the IL‐23 receptor and deficiency of IL‐12Rβ1 thus abolishes both IL‐12 and IL‐23 signaling. IL‐12Rβ1 deficiency is caused by bi‐allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL‐12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL‐12Rβ1 protein. In addition to disease‐causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the function of IL‐12Rβ1 and molecular genetics of human IL12RB1.

A rat mAb (NIM-R5) was prepared against a 42-kD B cell activation Ag (p42). The expression of p42 is increased upon activation. NIM-R5 induces an increase of intracellular Ca2+, due to influx from the exterior milieu via calcium channels. This stimulation does not prejudice further stimulation with anti-Ig, and thus p42 constitutes an activation signal independent of membrane Ig. The antibody induces increased expression of class II molecules on resting B lymphocytes and prepares the cells for "spreading" when interacted with immobilized anti-class II antibody. The antibody alone is weakly mitogenic and comitogenic with IL-4 on resting B cells. Of particular interest, NIM-R5 induces proliferation and rescue from apoptosis in B cells activated in vitro. In conclusion, NIM-R5 induces an Ig-independent activation and proliferation of resting and activated B cells. This antibody does not recognize other known B cell activation Ag such as CD23, CD40, or CD72. We therefore propose that the p42 Ag is a glycoprotein with an important role in the regulation of B lymphocyte activation and survival.