The Somatic Mutation Paradigm in Congenital Malformations: Hirschsprung Disease as a Model.

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception.

Isolation and molecular characterization of the B cells producing the paraprotein in a case of benign monoclonal gammapathy in C57BL mice.

Benign monoclonal gammapathy (BMG) is defined as a benign monoclonal B cell proliferative disorder characterized by the presence of a persisting component of homogenous immunoglobulins (H-Ig) in the serum. A possible role of antigenic stimulation in the development of BMG has been suggested. From a C57BL mouse, a murine model for BMG, we have isolated clonally related B cells in order to investigate the occurrence of somatic mutations in the variable heavy chain (VH) region of the genes of H-Ig-producing B cell clones.

Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ultrafiltered diet.

This study investigates the influence of exogenous antigenic stimulation on the serum immunoglobulin levels and the levels of circulating natural antibodies against carbohydrate antigens. Thus, BALB/c mice, raised in a germ-free environment and fed a chemically defined, ultrafiltered diet (GF-CD), were employed. These mice had normal serum IgM levels, but IgG and IgA levels were approximately 5% of conventionally reared littermates.

B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice. II. Analysis of antigen-binding capacities in relation to VH gene usage.

Hybridomas were derived from lipopolysaccharide-reactive splenic B cells of adult germ-free BALB/c mice fed a chemically defined ultrafiltered "antigen-free" diet (GF-CD) and from splenic B cells of 5-day-old conventional (CV-NEO) BALB/c mice. The monoclonal antibodies (mAb) from both collections of hybridomas were tested for reactivity against a large panel of antigens of exogenous and endogenous origin. As a source of natural exogenous antigens 36 different bacteria and 9 different viruses were used, while as endogenous antigens frozen tissue sections of stomach, liver and kidney, the Hep-2 cell line and the anti-idiotopic mAb Ac38 and Ac146 were used.

B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice. I. Preferential utilization of the CH-proximal VH gene family PC7183.

Early in ontogeny B cells preferentially use VH gene families which are most adjacent to the genes coding for the constant part of the immunoglobulin molecule. In conventional adult mice, however, a random usage of VH gene families has been found. We investigated the role of exogenous antigenic stimulation on this normalization of VH gene usage by B cells.