CD19 is a response regulator of B lymphocyte development, activation, and differentiation
CD19-deficient mice generate normal numbers of bone marrow B cells, but have decreased numbers of peripheral B cells with a dramatic loss within the Bl lineage. In contrast, transgenic mice that express human CD19 (hCD19) suggests a role for CD19 in early B cell clonal deletion since there is a significant decrease in the number of B cells generated within the bone marrow. CD19-deficient B cells are hyporesponsive to mitogenic stimulation and have decreased serum Ig levels while transgenic mice that overexpress CD19 are hyperresponsive. The role of CD19 in B cell growth regulation in vivo was examined further by generating mice expressing various densities of cell surface CD 19. Mice that expressed wild-type levels of hCD19 in the absence of endogenous mouse CD19 showed normal B cell development and function, including Bl cells. These mice also demonstrated normal serum Ig levels. In contrast, mice that overexpressed CD19 (2-3 fold) had significant defects in early B cell development of conventional B cells, dramatically increased numbers of Bl cells, augmented mitogenic responses and increased serum Ig levels. Thus, hCD19 can functionally replace mouse CD 19. In addition, slight changes in CD 19 receptor density dramatically affected B cell development as the number of B-l cells, proliferative responses, and serum Ig levels correlated with the surface expression levels of CD 19. These experiments suggest that CD 19 functions to define signaling thresholds for cell surface receptors that regulate B lymphocyte selection, activation and differentiation.
Sato, S; Ono, N; Steeher, DA; Tedder, TF
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