Biomedical subjects

Karin Reif

Publications and source records attributed to Karin Reif.

3 recordsLinked to original sources

PubMed2004

Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing.

Despite the established role for PI3Ks in cell migration, the PI3Ks involved in lymphocyte chemotaxis are poorly defined. In this study, we report that p110gamma-deficient T cells, but not B cells, show reduced chemotactic responses to the lymphoid chemokines, CCL19, CCL21, and CXCL12. As B cell and T cell chemotactic responses were both sensitive to the general PI3K inhibitors, wortmannin (WMN) and LY294002, we explored whether B cell responses were affected in mice lacking p110delta, a major PI3K isoform in lymphocytes. B cells deficient in p110delta showed diminished chemotactic responses, especially to CXCL13. Adoptive transfer experiments with WMN-treated wild-type B cells and with p110delta-deficient B cells revealed diminished homing to Peyer's patches and splenic white pulp cords. WMN selectively inhibited CXCR5-dependent B cell homing to Peyer's patches. These observations establish that p110gamma and p110delta function in lymphocyte chemotaxis, and show differential roles for PI3K family members in B and T cell migration.

Adoptive Transfer↗

PubMed2002

Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position.

B lymphocytes re-circulate between B-cell-rich compartments (follicles or B zones) in secondary lymphoid organs, surveying for antigen. After antigen binding, B cells move to the boundary of B and T zones to interact with T-helper cells. Despite the importance of B--T-cell interactions for the induction of antibody responses, the mechanism causing B-cell movement to the T zone has not been defined. Here we show that antigen-engaged B cells have increased expression of CCR7, the receptor for the T-zone chemokines CCL19 and CCL21, and that they exhibit increased responsiveness to both chemoattractants. In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone. Using retroviral-mediated gene transfer we demonstrate that increased expression of CCR7 is sufficient to direct B cells to the T zone. Reciprocally, overexpression of CXCR5, the receptor for the B-zone chemokine CXCL13, is sufficient to overcome antigen-induced B-cell movement to the T zone. These findings define the mechanism of B-cell relocalization in response to antigen, and establish that cell position in vivo can be determined by the balance of responsiveness to chemoattractants made in separate but adjacent zones.

Animals↗

PubMed2002

The CDM protein DOCK2 in lymphocyte migration.

T and B lymphocytes migrate hundreds of micrometers each day to survey the body's lymphoid tissues for antigens. No other mammalian cell type undergoes such extensive and continual movement, raising the question of whether lymphocytes have specializations to support their migratory behavior. This possibility has recently gained support from studies of mice deficient in DOCK2, a member of the Caenorhabditis elegans Ced-5, mammalian DOCK180 and Drosophila melanogaster myoblast city (CDM) family of scaffolding proteins. Migration of lymphocytes, but not other cell types, is severely disrupted in DOCK2-deficient mice. Despite the conserved role of CDM molecules in regulating Rac activation and actin assembly, relatively little is known about how these molecules function. Here, we review the role of DOCK2 in lymphocyte homing to lymphoid tissues and discuss recent findings for other CDM family molecules that provide a basis for understanding how DOCK2 might function in lymphocytes.

Animals↗