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

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

Dermatology-oncolog

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

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

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

IgD attenuates the IgM-induced anergy response in transitional and mature B cells

Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire