CD19: Lowering the Threshold for Antigen Receptor Stimulation of B Lymphocytes

Abstract

Lymphocytes must proliferate and differentiate in response to low concentrations of a vast array of antigens. The requirements of broad specificity and sensitivity conflict because the former is met by low-affinity antigen receptors, which precludes achieving the latter with high-affinity receptors. Coligation of the membrane protein CD19 with the antigen receptor of B lymphocytes decreased the threshold for antigen receptor-dependent stimulation by two orders of magnitude. B lymphocytes proliferated when approximately 100 antigen receptors per cell, 0.03 percent of the total, were coligated with CD19. The B cell resolves its dilemma by having an accessory protein that enables activation when few antigen receptors are occupied.

Differential adhesion pattern of B cell chronic lymphocytic leukemia cells

“…Our observation that the clone of anti-integrin ␣4 that was used (HP2/1) did not induce aggregation, was consistent also with the observations of Campanero et al 32 CD19, together with complement receptor CD21 (CR2), target of an antiproliferative antibody-1 (TAPA-1, CD81) and Leu-13, forms a functionally important membrane complex on B cells. [33][34][35] Each component of this complex independently regulates the activation, proliferation and function of B cells 18,36 and is able to initiate homotypic and heterotypic adhesion. [37][38][39] Aggregation of B cells could also be triggered by other cell surface molecules.…”

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

“…33 To detect the c.972insA The shaded area represents the normal range for healthy adult controls and was determined in a previous study. 13 (e, f) The avidity index of antirabies IgG1 was measured 4 weeks after primary and secondary vaccinations. Due to the low anti-rabies IgG1 levels, the avidity index could not be measured for CD19-deficient patient ID558.…”

“…5,6 CD19 forms a complex with CD21, CD81 and CD225, and functions to lower the threshold for B-cell antigen receptor (BCR) signaling following antigen engagement. 13 Consequently, CD19-deficient and CD81-deficient patients were found to be defective in BCR stimulation and showed poor responses to vaccination. 5,12 We identified a Turkish immunodeficient boy who is a cousin of the first identified Turkish CD19-deficient patient, and was homozygous for the same CD19 gene mutation (c.972insA).…”

Continuous signaling of CD 79b and CD 19 is required for the fitness of Burkitt lymphoma B cells

“…On activated B cells, however, the CD19 complex is found in close proximity to the open IgM‐BCR and thus gains access to ITAM signaling (Klasener et al , 2014). The IgM/CD19/CD81/CD21 complex is also stabilized by its co‐ligation with complement‐bound antigens that can reduce the threshold for BCR signaling 10‐ to 100‐folds (Carter & Fearon, 1992). The mouse CD19‐deficient B cells have defects in proliferation and maturation in peripheral lymph tissues and spleen, and have a defective T‐cell dependent antigen response (Rickert et al , 1995).…”