title: Chronic lymphocytic leukemia immunoglobulins display bacterial reactivity that converges and diverges from auto-/poly-reactivity and IGHV mutation status.
abstract: Chronic lymphocytic leukemia (CLL) is an incurable leukemia of unknown etiology. Multiple studies suggest that the structure of the variable domains of the surface IGs on these cells, and signaling through them, play key roles in developing the disease. Hence, CLL appears to be driven by antigen-BCR interactions, and identifying the selecting antigens involved in this process is an important goal. We studied the antigen-binding characteristics of 23 CLL-derived, recombinantly-expressed IGs with 5 pathogenic bacteria, determining that CLL IGs differ in bacterial reactivity based on IGHV gene use, mutation status, and association with IGHD and IGHJ genes ("stereotypy"). Although most bacterial-reactive IGs followed the paradigm that IGHV-unmutated IGs were more auto-/poly-reactive, several did not. In addition, some CLL IGs were bacterial mono-reactive, and these displayed IGKV use biases. These findings are consistent with CLL B cells being driven into the leukemogenic process by bacterial as well as auto- antigens.
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA.
authors: Katerina
authors: K
authors: Hatzi
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA.
authors: Rosa
authors: R
authors: Catera
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA.
authors: Carolina
authors: C
authors: Moreno Atanasio
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA.
authors: Vincent A
authors: VA
authors: Fischetti
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors: Steven L
authors: SL
authors: Allen
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors: Jonathan E
authors: JE
authors: Kolitz
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors: Kanti R
authors: KR
authors: Rai
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors: Charles C
authors: CC
authors: Chu
authors: The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA. Electronic address: NChizzi@Northwell.edu.
authors: Nicholas
authors: N
authors: Chiorazzi
mesh_terms: D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D016972:Enterobacter cloacae / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D056546:Lactobacillales / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D009154:Mutation
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
keywords: Antibody; Autoantigen; B lymphocyte; B-cell antigen receptor; Bacteria; Chronic; Lymphocytic Leukemia