Defects in B Lymphocyte Maturation and T Lymphocyte Activation in Mice Lacking Jak3

Abstract

Biochemical studies of signaling mediated by many cytokine and growth factor receptors have implicated members of the Jak family of tyrosine kinases in these pathways. Specifically, Jak3 has been shown to be associated with the interleukin-2 (IL-2) receptor gamma chain, a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Mice lacking Jak3 showed a severe block in B cell development at the pre-B stage in the bone marrow. In contrast, although the thymuses of these mice were small, T cell maturation progressed relatively normally. In response to mitogenic signals, peripheral T cells in Jak3-deficient mice did not proliferate and secreted small amounts of IL-2. These data demonstrate that Jak3 is critical for the progression of B cell development in the bone marrow and for the functional competence of mature T cells.

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

“…However, it remains unproven which JAK is responsible for phosphorylation of IL2Rb vs Stat5 proteins in vivo. What is clear, however, is that both JAKs are required for normal IL-2-mediated Stat5 activation (Nosaka et al, 1995;Park et al, 1995;Rodig et al, 1998;Thomis et al, 1995).…”

A Profound Deficiency in Thymic Progenitor Cells in Mice Lacking Jak3

“…Studies of gene-targeted mice have provided much of the evidence implicating specific cytokines in ␣␤ T cell, ␥␦ T cell, or NK cell development. For instance, mice lacking IL-7 or components of the IL-7R signaling pathway (i.e., IL-7R␣, common ␥-chain (␥c), 3 or Jak3) fail to develop ␥␦ T cells (1)(2)(3)(4)(5)(6)(7). IL-15R signaling has been shown to be critical for NK cell development, as IL-15R␣-, ␥c-, and Jak3-deficient mice all lack NK cells (4 -10).…”

“…Jak3 Ϫ/Ϫ , IL-7 Ϫ/Ϫ , and IL-7R␣ Ϫ/Ϫ mice have been described previously (7,11,12) and were bred and maintained under specific pathogen-free conditions. IL-7R␣ ϩ/Ϫ mice were a kind gift of Rachel Gerstein (University of Massachusetts Medical School, Worcester, MA), and IL-7 Ϫ/Ϫ mice were a kind gift of Richard Murray (DNAX, Palo Alto, CA).…”

Characterization and Analysis of the Proximal Janus Kinase 3 Promoter

“…Jak3 Ϫ/Ϫ mice also have profound immunodeficiency, but the phenotype is somewhat different from that of human Jak3 deficiency. These mice lack B cells and have small numbers of T cells, which also have an activated phenotype (12).…”