CD19 cytoplasmic tyrosine residues Y482 and Y513 are sufficient to promote normal B cell development and differentiation but induce a skewed humoral immune response.

Abstract

Abstract CD19 amplifies BCR signal transduction by recruiting SH2 domain-containing proteins to its nine cytoplasmic phosphorylated tyrosine residues. Previous studies have shown that Y482 and Y513, which recruit PI3K are required for normal B cell development/differentiation and a productive T-dependent humoral response. However, it has not been determined if CD19 Y482 and Y513 are sufficient to promote normal B cell differentiation or antibody response to immunization. Furthermore, the effects of upstream CD19 tyrosine-mediated Vav/PLCγ2 and Grb2/Sos signaling are not well characterized. Using mice expressing CD19 mutated to only express tyrosines Y482 and Y513, we demonstrate that CD19 mediated Lyn/PI3K signaling is sufficient for B1 B cell development, marginal zone B cell maturation, and germinal center B cell formation. However, these mice exhibit an increased antibody response against T-independent antigens and are impaired in their ability to generate class-switched germinal center B cells during a T-dependent immune response, as well as long-lived, class-switched antibody secreting cells. These findings suggest that cross-talk between signal effectors recruited to Y482 and Y513 and those recruited to other CD19 tyrosine residues is important for determining the qualitative nature of the humoral response.