CD19 Function in Central and Peripheral B-Cell Development

Abstract

Although the B-cell antigen receptor (BCR) factors most prominently in the maintenance and differentiation of mature B cells, it is now appreciated that co-receptor molecules can positively or negatively modulate signals through the BCR. Co-receptors are functionally defined as modifiers of BCR engagement and signal transduction, and are distinct from other accessory molecules that act independently to regulate B-cell growth. The co-receptor CD19 functions to augment signals by the pre-BCR/BCR and in doing so can modulate B-cell fate decisions at multiple stages of development. In mature B cells, CD19 also associates with complement receptor 2 (CR2/CD21) and is pivotal for transducing signals induced by co-recognition of complement C3d-fixed antigens by the BCR and CD21. In this article, we focus on recent progress in the understanding of CD19 function through the characterization of mouse models that relate in vivo function to biochemical properties of CD19.

CD86 Regulates IgG1 Production via a CD19-Dependent Mechanism

“…CD19 contains nine tyrosine residues in the cytoplasmic domain that are phosphorylated to promote CD19 interaction with a number of SH2 domain-containing proteins, including Lyn, Vav, Grb2, and p85␣ PI3K (reviewed in Ref. 23). To determine whether CD86 stimulation increased tyrosine phosphorylation of CD19, Western blot analysis was performed on whole cell lysates from B cells activated as described above.…”

“…CD19 is a coreceptor primarily expressed on the B cell and plays an important role in B cell development, as well as BCR-and CD21-induced signal transduction (23). CD19-deficient mice show abnormal B-1 cell development and impairment of T celldependent Ab responses in vivo (24,25).…”

“…The cytoplasmic tail of CD19 contains nine tyrosine residues, that when phosphorylated, allow for the interaction with the SH2 domain-containing proteins, including Lyn, Vav, Grb2, and p85␣ PI3K (reviewed in Ref. 23). Lyn is one protein tyrosine kinase (PTK) that phosphorylates CD19 (31) and is reported to play both a positive and negative role in regulating B cell activation (32).…”

CD19 regulates ADAM28‐mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells

“…The biochemical basis for signal augmentation by CD19 is becoming clearer, yet still needs more information on the specific and important roles for CD19 as a signal‐transducing component for receptors other than the BCR 31. We showed here that CD19 could regulate Notch2 (Fig.…”

“…In recent years, considerable progress has been made in deciphering the function of CD19 in mature FO and MZ B‐cell generation 31. CD19 −/− mice exhibit three striking deficiencies in peripheral B‐cell subsets: ( i ) B‐1 cells, ( ii ) MZ B cells and ( iii ) GC B cells 12, 32, 33.…”