Homeodomain-interacting protein kinase (HIPK)-1 is required for splenic B cell homeostasis and optimal T-independent type 2 humoral response.

The homeodomain-interacting protein kinase (HIPK) family is comprised of four highly related serine/threonine kinases originally identified as co-repressors for various homeodomain-containing transcription factors. The HIPKs have been shown to be involved in growth regulation and apoptosis, with numerous studies highlighting HIPK regulation of the tumor suppressor p53. In this study, we have discovered a B cell homeostatic defect in HIPK1-deficient (HIPK1(-/-)) mice.

The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation.

Interleukin-7 (IL-7) plays several important roles during B cell development including aiding in; the specification and commitment of cells to the B lineage, the proliferation and survival of B cell progenitors; and maturation during the pro-B to pre-B cell transition. Regulation and modulation of IL-7 receptor (IL-7R) signaling is critical during B lymphopoiesis, because excessive or deficient IL-7R signaling leads to abnormal or inhibited B cell development. IL-7 works together with E2A, EBF, Pax-5 and other transcription factors to regulate B cell commitment, while also functions to regulate Ig rearrangement by modulating FoxO protein activation and Rag enhancer activity.

Seasonal H1N1 influenza virus infection induces cross-protective pandemic H1N1 virus immunity through a CD8-independent, B cell-dependent mechanism.

During the 2009 H1N1 influenza virus pandemic (pdmH1N1) outbreak, it was found that most individuals lacked antibodies against the new pdmH1N1 virus, and only the elderly showed anti-hemagglutinin (anti-HA) antibodies that were cross-reactive with the new strains. Different studies have demonstrated that prior contact with the virus can confer protection against strains with some degree of dissimilarity; however, this has not been sufficiently explored within the context of a pdmH1N1 virus infection. In this study, we have found that a first infection with the A/Brisbane/59/2007 virus strain confers heterologous protection in ferrets and mice against a subsequent pdmH1N1 (A/Mexico/4108/2009) virus infection through a cross-reactive but non-neutralizing antibody mechanism.

Modulation of IL-7 thresholds by SOCS proteins in developing B lineage cells.

During B lymphopoiesis, IL-7 induces survival, proliferation, and differentiation signals that are important during the pro-B to pre-B cell transition. We showed that murine small pre-B stage cells do not signal or proliferate in response to IL-7, yet they maintain IL-7R surface expression. Loss of proliferative responsiveness to IL-7 is mediated by suppressor of cytokine signaling protein 1 (SOCS-1), the expression of which is regulated during B lymphopoiesis, with the highest levels observed in small pre-B cells.

Targeted deletion of the tachykinin 4 gene (TAC4-/-) influences the early stages of B lymphocyte development.

Hemokinin-1 (HK-1), encoded by the TAC4 gene, is a tachykinin peptide that is predominantly expressed in non-neuronal cells, such as immune cells. We have disrupted the mouse TAC4 gene to obtain a better understanding of the actions of HK-1 during hematopoiesis. We demonstrate here that TAC4(-/-) mice exhibit an increase of CD19(+)CD117(+)HSA(+)BP.

Heparan sulfate and heparin enhance ERK phosphorylation and mediate preBCR-dependent events during B lymphopoiesis.

As B lineage cells develop, they interact with cells, proteins, and extracellular matrix components of the surrounding microenvironment. In vitro, one critical checkpoint for developing cells occurs as they lose responsiveness to IL-7. These cells require contact with either stromal cells or other B lineage cells to mature.

Generation and characterization of stromal cell independent IL-7 dependent B cell lines.

In-vitro B cell cultures have played a significant role in the study of B cell development. Their utility in developmental and biochemical studies, however, has been limited by the challenges associated with obtaining and maintaining adequate cell numbers of pure and/or rare populations. Although B cell lines allow for circumvention of some of these issues, they have traditionally been generated via viral infection or genetic transformation and are thus less representative of in-vivo cells.

Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes.

Selective interference with the CD45RB isoform by mAb (anti-CD45RB) reliably induces donor-specific tolerance. Although previous studies suggest participation of regulatory T cells, a mechanistic understanding of anti-CD45RB-induced tolerance is lacking. We report herein the unexpected finding that tolerance induced by this agent is not established in B cell-deficient mice but can be recovered by preemptive B lymphocyte transfer to B cell-deficient hosts.