PRIMARY CUTANEOUS DIFFUSE LARGE B-CELL LYMPHOMA, LEG TYPE, EXPRESS STEREOTYPED B-CELL RECEPTORS WITH UNIQUE NONSYNONYMOUSLY MUTATED CONSTANT REGIONS

Dermatology-oncolog

Insulin-like Growth Factor 1 Receptor (IGF1R) - A novel therapeutic target in chronic lymphocytic leukemia

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Insulin-like growth factor-1 receptor (IGF1R) as a novel target in chronic lymphocytic leukemia

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Antigen-Independent, Autonomous B-Cell Receptor Signaling As a Dominant Candidate Oncogenic Mechanism in ABC DLBCL

Dermatology-oncolog

Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Efficient generation of B lymphocytes by recognition of self-antigens

Antibody diversity is generated by a random gene recombination process with the inherent risk of the production of autoreactive specificities. The current view suggests that B cells expressing such specificities are negatively selected at an early developmental stage. Using the knock-in model system of the 3–83 autoreactive B-cell antigen receptor (BCR) in combination with precursor-BCR (pre-BCR) deficiency, we show here that the 3–83 BCR mediates efficient generation of B cells in the presence, but not the absence, of a strongly recognized auto-antigen. Experiments with mixed bone marrow chimeras showed that combining the 3–83 BCR with the corresponding auto-antigen resulted in efficient reconstitution of B-cell development in immune-deficient mice. These results suggest that B cells are positively selected by recognition of self-antigens during developmental stages that precede receptor editing. Moreover, the data indicate that the pre- BCR functions as a specialized autoreactive BCR to initiate positive selection at a stage where the cells express immunoglobulin heavy but not light chains