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Identifier

000426733

Title

Study of the interactions between the clonotypic immunoglobulin and antigens in mature B cell neoplasms

Alternative Title

Μελέτη της αλληλεπίδρασης των κλωνοτυπικών ανοσοσφαιρινών με αντιγόνα σε νεοπλάσματα από ώριμα Β λεμφοκύτταρα

Author

Τυριτίδης, Ιωάννης

Thesis advisor

Παπαδάκη, Ελένη

Reviewer

Σταματόπουλος, Κώστας
Σπηλιανάκης Χαράλαμπος

Abstract

Analysis of the clonotypic B cell Receptor (BcR) immunoglobulins (IG) has been critical for understanding the molecular basis of mature B cell malignancies, supporting the notion of antigen selection in lymphomagenesis. However, despite relevant progress, the exact nature of the implicated antigens remains elusive. On these grounds, definition of the antigens recognized by the BcR IGs expressed by the malignant cells is crucial for elucidating the in vivo stimulation of the leukemic cells and could shed light on the ontogeny of B cell malignancies. In the present study we examined 2 types of B cell malignancies: Chronic Lymphocytic Leukemia (CLL) and Splenic Marginal Zone Lymphoma (SMZL). The clonotypic BcR IGs from 41 CLL and 12 SMZL patients were produced as recombinant monoclonal antibodies (mAbs) and their antigenic specificity profiles were assessed by ELISA and flow cytometry. In particular, the reactivity against a variety of autoantigens already shown to be common targets of natural and disease occurring antibodies (dsDNA, actin, myosin, thyroglobulin, β-amyloid, carbonic anhydrase, F(ab’)2 fragment of human IgGs, the non-self hapten TNP) was assessed by ELISA. In addition, recognition of epitopes on the surface of viable HEK293T cells was evaluated by flow cytometric analysis. One or more of the above antigens were recognized by the CLL mAbs derived from patients with aggressive disease, as well as many SMZL mAbs. This pattern of antigenic recognition is reminiscent of that of natural and disease occurring antibodies. However, differences in the reactivity pattern were observed between mAbs derived from CLL patients assigned to distinct disease subsets as well as between the two distinct entities, implying differences in the antigen exposure history and/or in the subsequent immune responses to the cognate (auto)antigen(s). Finally, until recently the constant region of the immunoglobulins was considered responsible for the antigen fine specificity. However, recent studies highlight the role of the immunoglobulin constant region in the regulation of the antigen recognition. In the current thesis we showed that isotype switching and subsequently the constant region affect the antigenic specificity/affinity of CLL BcR IGs too.

Language

English

Subject

B cell receptor

Chronic lymphocytic leukemia

Splenic marginal zone lymphoma

Β κυτταρικός υποδοχέας

Σπληνικό λέμφωμα οριακής ζώνης

Χρόνια λεμφοκυτταρική λευχαιμία

Issue date

2019-12-11

Collection