Cutaneous lymphomas
Franco Cavalli, Harald Stein, Emanuele Zucca in Extranodal Lymphomas, 2008
The immunophenotype of cutaneous MZL is similar to that seen in other sites. The B-cell associated antigens CD20 and CD79a are generally expressed. The cells are negative for the germinal center-associated markers CD10 and BCL-6. Plasmacytic differentiation correlates with the expression of cytoplasmic immunoglobulin. The plasma cells may be monotypic and in cutaneous lesions monotypic plasma cells are most readily identified in the very superficial dermis. Cases in which the light-chain class changes over time have been observed. In some cases, restricted light-chain expression may be identified in the absence of clonality by immunoglobulin heavy-chain PCR. Whether such lesions are truly lymphomas is difficult to establish with certainty.33
The Non-Hodgkin’s Lymphomas and Plasma Cell Dyscrasias
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
The immunophenotype of plasma cell myeloma and plasmacytoma is similar to benign plasma cells. Like benign plasma cells, the neoplastic cells express cytoplasmic, but not surface, immunoglobulin. However, unlike reactive process, which contains a mixture of kappa-and lambda-positive plasma cells, neoplastic plasma cells express monoclonal immunoglobulin and show a light chain restriction. A population is said to demonstrate a light chain restriction when the ratio of one light chain type to the other exceeds 16:1. Both benign and malignant plasma cells fail to express most B-cell-associated antigens, such as CD19, CD20, and CD22. However, they express the B-cell-associated antigen CD79a, which is also expressed on plasma cells. Like benign plasma cells, the neoplastic cells are usually negative for CD45 (leukocyte common antigen), positive for CD38 and the mature plasma cell antigens, PC-1, and PCA-1. They also may express epithelial membrane antigen (EMA). Neoplastic plasma cells, but not benign plasma cells, stain with the antibody MB2, and also often epxress CD56, an adhesion molecule that is associated with natural killer cell differentiation. A minority of cases express CD10 (CALLA), and markers of myelomonocytic differentiation, such as CD11b, CD11c, CD13, CD15, and CD33.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Gabriel Virella in Medical Immunology, 2019
The B cell receptor (BCR) complex is constituted by sIg associated with CD79a/Igα) and CD79b/Igβ (Figure 10.3). Antigen recognition occurs though the sIg, whereas Igα and Igβ mediate signal transduction. After antigen binding, the recruitment of tyrosine kinase to the cytoplasmic domains of Igα and Igβ initiates the activation cascade. The major kinase that is recruited to the BCR complex is Bruton's tyrosine kinase (Btk). Congenital Btk deficiency is associated with a block in B-cell differentiation, demonstrating that signals delivered through the fully assembled BCR and associated kinases are necessary for B cell development during ontogeny.
Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy
Published in Expert Review of Hematology, 2022
Salvatore Perrone, Paolo Lopedote, Mario Levis, Alice Di Rocco, Stephen Douglas Smith
Antibody-drug conjugates represent a major class of novel therapies in lymphoma, and offer the potential for targeted delivery of chemotherapy agents to malignant cells expressing B-cell specific surface antigens. The CD79 molecule, is a heterodimer composed of an Igα (CD79a) and Igβ (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and it appears before the pre-B-cell stage, and the CD79a chain can still be present at the plasma cell stage [59]. Polatuzumab vedotin-piiq (pola) in combination with BR was approved in 2019 by the FDA and the EMA (Figure 2) for r/r DLBCL who failed ≥2 lines of therapy, for the results of the GO29365 trial and is now incorporated in the National Cancer Care Network (NCCN) guidelines for patients in this setting [60].
Polatuzumab vedotin for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma
Published in Expert Opinion on Biological Therapy, 2021
Mary-Kate Malecek, Marcus P. Watkins, Nancy L. Bartlett
Polatuzumab vedotin (Genentech, South San Francisco, CA, USA) is an ADC comprised of an anti-CD79b monoclonal antibody conjugated to monomethyl auristatin (MMAE), a microtubule-disrupting cytotoxin (Box 1). CD79b is a signaling component of the B cell receptor (BCR) complex and is expressed almost exclusively on normal and malignant B cells [53]. CD79a and CD79b expression precedes CD20 expression and disappears in later stages of B cell ontogeny. BCR cross-linking triggers signaling, targeting it to the lysosome-like major histocompatibility complex class II positive compartment. This allows ADC internalization, lysosomal degradation of the linker, and release of the drug only in the targeted cells. CD79b is expressed in DLBCL, mantle cell lymphoma, Burkitt lymphoma, and follicular lymphoma , and is, therefore, an appealing target for the development of novel therapeutics [54].
S3Ab, a novel antibody targeting B lymphocytes, is a potential therapeutic agent for B-lineage malignancies
Published in Journal of Drug Targeting, 2019
Sisi Li, Hongqiang Shen, Qiang Shu
In order to further determine the targeted antigen of S3 is the extracellular domain of CD79α, we identified the reaction of recombinant S3 monomer with CD79α extracellular protein. First, we obtained the DNA sequence of the S3 antibody and searched in the National Centre for Biotechnology Information (NCBI) database. The results showed heavy chain variable region of S3 (VHS3) has a total length of 114 amino acids and the 22nd and 96th positions are characteristic Cys (cysteine). The light chain variable region of S3 (VLS3) has a total length of 112 amino acids and the 23rd and 93rd positions are characteristic Cys. The DNA sequence of S3 was inserted into a pTT5 plasmid. Then, we transfected the plasmid into CHO-3E7 cells, the recombinant S3 monomer was expressed by host cells. The result of IP showed the recombinant S3 monomer recognised the same antigen banding of 33 KDa with the parent S3 and the flow cytometry showed it retained a strong binding activity to its antigen and could significantly block the binding of murine S3 to the antigen. The standard CD79α extracellular protein was purchased from American ABCAM Company (Cat. No.: ab112267), the amino acid sequence of which is composed as follows: LWMHKVPASLMVSLGEDAHFQCPHNS SNNANVTWWRVLHGNYTWPPEFLGPGEDPNGTLIIQNVNKSHGGIYVCRVQEGNESYQQSCGTYLRVRQPPPRPFLDMGEGT (see https://www.abcam.com/recombinant-human-cd79a-protein-ab112267.html for details).
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