Though most mutations are deleterious, an interplay between somatic mutation and selection within germinal centers (GC) results in rapid generation of high a nity memory B cells. How high a nity B cells with large numbers of mutations are generated and preserved, within GC containing at their peak only a few thousand cells, has been puzzling. We have developed a model of somatic mutation and B ...

Hematopoietic stem cell transplantation is characterized by a prolonged period of humoral immunodeficiency. We have previously shown that the deficiencies are probably not due to the failure to utilize the appropriate V regions in the pre-immune repertoire. However, a striking observation, which correlated with the absence of immunoglobulin IgD(-) cells and was consistent with a defect in antig...

Sequencing the complete factor IX gene of 2 sisters with hemophilia B with different phenotypes and no family history of hemorrhagic diathesis revealed a common 5' splice site mutation in intron 3 (T6704C) in both and an additional missense mutation (I344T) in one. The presence of dysfunctional antigen in the latter strongly suggested that these mutations are in trans. Neither mutation was foun...

The pivotal role played by antigen in the clonal selection of B cells for initial participation in an immune response is well established. Antigen selective mechanisms ensure that antigen-binding antibodies are produced during all stages of the immune response. However, antibodies that lack specificity for the immunogen might also be produced during the course of an antigen-driven immune respon...

The genes controlling either Escherichia coli somatic antigen 8 or 25 were conjugally transferred to virulent Shigella flexneri 2a recipients to determine whether the aquisition of these antigens would affect the virulence of the resulting hybrid. A high proportion of such hybrids were found to be rough and hence were avirulent. Some smooth S. flexneri hybrids which replaced their native group ...

B cells use translesion DNA synthesis (TLS) to introduce somatic mutations around genetic lesions caused by activation-induced cytidine deaminase. Monoubiquitination at lysine(164) of proliferating cell nuclear antigen (PCNA(K164)) stimulates TLS. To determine the role of PCNA(K164) modifications in somatic hypermutation, PCNA(K164R) knock-in mice were generated. PCNA(K164R/K164R) mutants are b...

Recent genomic studies have outlined a landscape of recurrent alterations within some subtypes of lymphoid cancer. Yet, the timing and cellular contexts during which these alterations occur (ie, the molecular ontogeny) remain poorly understood. Lymphoid malignancies offer an exceptional opportunity to delineate the ontogeny of somatic alterations, as lymphocyte differentiation absolutely requir...

Mouse chromosome 12 encodes the heavy chains of immunoglobulins (Igh), a family of T cell surface molecules, and a tumor antigen that may be homologous to immunoglobulins. To refine and extend the genetic map of this chromosome, a procedure has been developed to isolate chromosome 12-specific DNA fragments from a somatic cell hybrid carrying the chromosome on a Chinese hamster background. Five ...

Porcine dermatitis and nephropathy syndrome (PDNS) is a sporadic, usually fatal disease of growing and finishing pigs that has been recognized in many pig-producing countries. Pasteurella multocida strains isolated from 15 pigs with PDNS and 51 pigs without PDNS were characterized by capsule and somatic antigen typing, random amplified polymorphic DNA (RAP-D) typing, and restriction analysis of...

This paper describes the application of an artificial immune system to a scheduling application. A novel approach multi-modal immune algorithm is proposed for finding optimal solutions to job-shop scheduling problems emulating the features of a biological immune system. Inter-relationships within the proposed algorithm resemble antibody molecule structure, antibody–antigen relationships in term...