Biomedical subjects

Annaiah Cariappa

Publications and source records attributed to Annaiah Cariappa.

4 recordsLinked to original sources

PubMed2004

Positive selection and lineage commitment during peripheral B-lymphocyte development.

Although it is appreciated that the antigen receptor on B cells is required for peripheral B-lymphocyte development and survival, it has been unclear whether this receptor interacts with self-antigens during development or if it signals constitutively in an antigen-independent fashion. The analysis of mutant mice in which antigen receptor signaling in B cells is either attenuated or enhanced has revealed the existence of a follicular versus marginal zone B-lymphocyte cell-fate decision. These analyses indicate that weak antigen receptor-derived signals favor marginal zone B-cell generation, and relatively strong signals favor the development of mature follicular B cells. Even stronger signals derived from the antigen receptor favor the generation of B1 B cells. This signal strength model for B-cell development supports the notion that self-antigens of varying affinity may mediate positive selection and lineage commitment. Direct evidence supporting such a view has been obtained from the analysis of antigen receptor knockin mice. Specific antigen receptors guide B cells to develop into specific lineages. Although Notch-2, nuclear factor-kappaBp50, and other genes are essential for marginal zone B-cell development, instructive signals delivered by the antigen receptor represent the primary force driving positive selection and lineage commitment in B lymphocytes.

Animals↗

PubMed2003

A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development.

Protein kinase C-associated kinase (PKK)/receptor interacting protein 4 (RIP4) is a protein kinase C (PKC) beta-associated kinase that links PKC to NF-kappaB activation. The kinase domain of PKK is similar to that of RIP, RIP2, and RIP3. We show in this study that PKK is expressed early during lymphocyte development and can be detected in common lymphoid progenitor cells. Targeting of a catalytically inactive version of PKK to lymphoid cells resulted in a marked impairment in pro-B cell generation in the bone marrow. Although peripheral B cell numbers were markedly reduced, differentiation into follicular and marginal zone B cells was not defective in these mice. B-1a and B-1b B cells could not be detected in these mice, but this might be a reflection of the overall defect in B cell production observed in these animals. In keeping with a possible link to PKCbeta, peripheral B cells in these mice exhibit a defect in anti-IgM-mediated proliferation. These studies suggest that PKK may be required early in B cell development and for BCR-mediated B cell proliferation.

Animals↗

PubMed2002

Defective proliferative responses in B lymphocytes and thymocytes that lack neurofibromin.

Nf1(-/-) fetal liver cells were used to reconstitute B and T cells in Rag-1(-/-) mice. Lymphocyte development was largely unimpaired in the absence of neurofibromin. However antigen-receptor induced proliferation was defective in neurofibromin deficient peripheral B cells and CD4(+) single positive thymocytes. In contrast to its role as a negative regulator of proliferation in many other cell types, neurofibromin may be a positive regulator of lymphocyte proliferation. Peripheral B cells exhibited circumscribed defects in anti-IgM induced protein tyrosine phosphorylation, which may contribute to the unexpected proliferative defect seen in these cells.

Animals↗

PubMed2002

Antigen-dependent B-cell development.

There is growing evidence that the development of naïve B cells depends on the interaction of self antigens with the BCR. A view that has emerged over the past year is that BCR signal output contributes in a large part to the developmental fate of peripheral B cells. Differences in antigen-receptor signal strength may determine whether B cells assume a marginal zone, follicular or B-1 phenotype.

Animals↗