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Identifier

000419908

Title

Production and study of monoclonal antibodies from patients with mature B cell neoplasms

Alternative Title

Παραγωγή και μελέτη μονοκλωνικών αντισωμάτων από ασθενείς με νεοπλάσματα από ώριμα Β λεμφοκύτταρα

Author

Καραγιάννη, Αικατερίνη

Thesis advisor

Σταματόπουλος, Κωνσταντίνος

Reviewer

Παπαδάκη, Ελένη
Χαμηλός, Γεώργιος

Abstract

Molecular studies of the clonotypic B cell Receptor (BCR) immunoglobulins (IGs) have contributed significantly to understanding the molecular basis of malignancies of mature B cells (B cell non-Hodgkin lymphomas, B-NHLs) and cemented the idea of antigen selection in disease ontogeny and evolution. However, despite recent progress, exactly which antigens are selecting and perhaps even continuously stimulating the malignant clones still remains to be elucidated. The present study focused on 2 types of B-NHL, namely Chronic Lymphocytic Leukemia (CLL) and Splenic Marginal Zone Lymphoma (SMZL). Clonotypic BCR IGs were produced as recombinant IgM monoclonal Antibodies (mAbs) from 8 SMZL and 34 CLL patients. Recombinant mAbs were profiled for antigen reactivity using ELISA assays, flow cytometric analysis and Western blot analysis. First, we noted that cases belonging to the same CLL stereotyped subset [subsets of cases expressing (quasi) identical BCRs] exhibited similar antigen reactivity profile. Interestingly, we also found that only mAbs from CLL cases with unmutated IGHV genes (U-CLL), generally associated with aggressive disease, exhibited a detectable anti-nuclear antibody (ANA) reactivity. Moreover, mAbs from indolent CLL cases with mutated IGHV genes but not aggressive U-CLL cases bound to the surfaces of viable leukemic MEC1 cells. In SMZL, our studies revealed recognition of nuclear and cytoplasmic antigens by SMZL mAbs expressing the most common IG gene rearrangements, thus suggesting that SMZL B cell clones may arise from polyreactive B cells in the splenic marginal zone. Interestingly, SMZL mAbs generally showed a stronger anti-dsDNA reactivity and a tendency for a higher ANA reactivity compared to CLL mAbs. This observation implies differences in the antigen exposure history and/or in the subsequent immune responses between the malignant B cells and/or the pre-malignant B cell progenitors of these two distinct entities.

Language

English

Subject

Antigens

B cell receptor

Chronic lymphocytic leukemia

Cloning

Splenic marginal zone lymphoma

Stereotypy

Αντιγόνα

Β κυτταρικός υποδοχέας

Κλωνοποίηση