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. 2021 Mar 23;5(4):e550.
doi: 10.1097/HS9.0000000000000550. eCollection 2021 Apr.

A Major Subset of Mutated CLL Expresses Affinity-selected and Functionally Proficient Rheumatoid Factors

Affiliations

A Major Subset of Mutated CLL Expresses Affinity-selected and Functionally Proficient Rheumatoid Factors

Jerry Janssen et al. Hemasphere. .
No abstract available

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Figures

Figure 1.
Figure 1.
The BCRs of CLLs with RF reactivity are affinity-selected and mediate tumor cell proliferation in response to ligation by human IgG. (A), Six out of 152 CLL IgM specifically bind IgG in ELISA. Controls are IgM of CLL57, which is polyreactive, and IgM (V3-7Sh-1) of CLL82, which is specific for β-(1,6)-glucan. (B), IgG-binding affinities of IgMs derived from the CLLs, including CLL115 and CLL189, and their IGHV-germline-reverted variants (CLL115-VH-GL, CLL189-VH-GL) as measured by surface plasmon resonance (IBIS MX96, IBIS Technologies, The Netherlands). (C), Binding characteristics of IgMs from CLL115, CLL115-GL, CLL189, and CLL189-GL with coated IgG in ELISA. (D), Primary cells of CLL189, CLL243, and CLL253 proliferate upon interaction with their cognate antigen (IgG) or with anti-IgM monoclonal antibodies. Fresh CLL cells were labelled with CFSE, cultured for 8 days and analyzed by flow cytometry. BCRs = B-cell receptors; CFSE = carboxyfluorescein succinimidyl ester; CLLs = chronic lymphocytic leukemias; IGHV = immunoglobulin heavy chain variable region; RF = rheumatoid factor.
Figure 2.
Figure 2.
The configuration of IGHV and IGKV of RF CLL. (A), IGHV and IGKV rearrangements and VH-CDR3 of 6 RF CLLs. (B), Alignment of amino acid sequences of the IGHV1-69-, IGHV3-30-, and IGKV3-20-expressing CLLs. Indicated in red a S36R shared between 4 CLL. (C), Comparison of the VH-CDR3 amino acid sequences expressed by CLL226, a salivary gland MALT lymphoma, and an ocular adnexal MALT lymphoma, respectively. VH-CDR3 homology is calculated as the fraction of identical/similar amino acids. Identical amino acids are depicted in red and similar amino acids are depicted in blue. CLLs = chronic lymphocytic leukemias; IGHV = immunoglobulin heavy chain variable region; IGKV = immunoglobulin kappa chain variable region; RF = rheumatoid factor.

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