Cryptic polyreactivity of IgG expressed by splenic marginal zone B-cell lymphoma.
Polyreactive antibodies represent a significant fraction of immune repertoires and play an important role in the immune defense and immune homeostasis. Polyreactive B-cell receptors (BCR), however, are frequently expressed by B-cell lymphomas. It was suggested that polyreactive BCR on lymphoma cells might deliver stimulation signals by binding to various endogenous or exogenous antigens, thus promoting the survival of the malignant cells. In addition to natural polyreactive antibodies, immune repertoires contain antibodies that acquire polyreactivity after exposure to different redox-active substances such as reactive oxygen species, iron ions and heme. Here, we demonstrate that an antibody cloned from a patient's splenic marginal zone B-cell lymphoma acquires physiologically relevant binding affinity to various autoantigens following exposure to heme. We elucidated the mechanisms underlying polyreactive antigen binding. The results obtained in this study imply that antigen-binding receptors expressed on some malignant cells acquire polyreactivity after exposure to redox substances that are released at sites of inflammation or as a result of cellular damage. The acquisition of novel BCR specificities under hemolytic or inflammatory conditions may play an important role in the physiopathology of certain B-cell malignancies.
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France; Université de Technologie de Compiègne, Compiègne Cedex, France.
Ankit
A
Mahendra
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Bagirath
B
Gangadharan
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Sébastien
S
André
AP-HP, Laboratoire d'Hématologie, Hôpital Pitié-Salpêtrière, Paris, France.
Myriam
M
Boudjoghra
Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; AP-HP, Laboratoire d'Hématologie, Hôpital Pitié-Salpêtrière, Paris, France.
Frédéric
F
Davi
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Maxime
M
Lecerf
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Cyril
C
Planchais
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Srinivas V
SV
Kaveri
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France.
Sébastien
S
Lacroix-Desmazes
INSERM, UMR S 1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S 1138, Paris, France; Université Paris Descartes, UMR S 1138, Paris, France. Electronic address: jordan.dimitrov@crc.jussieu.fr.
Jordan D
JD
Dimitrov
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D004151:Dipeptides / Q000276:immunology*; D005260:Female; D006427:Hemin / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology*; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017422:Sequence Analysis, DNA
D000906:Antibodies; D001324:Autoantigens; D004151:Dipeptides; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011947:Receptors, Antigen, B-Cell; C065126:N-(8-amino-1-carboxyoctyl)-alanyl-proline; D006427:Hemin
Antibody polyreactivity; B cell lymphoma; Heme; Hemolysis; Immunoglobulins