IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells

Cancer therapy using unconjugated monoclonal antibodies (mAb) has been limited by the lack of immune effector function of the mAb and antigenic modulation. JD118 is a cytotoxic murine IgM mAb with reactivity restricted to a subset of normal B cells, some monocytic series cells, and a large percentage of B cell hematopoietic neoplasms including acute and chronic leukemias and lymphomas. Specificity was determined on several hundred normal and neoplastic, hematopoietic and non-hematopoietic cells and tissues, as well as progenitor cells. JD118 was able to kill fresh human leukemias and lymphomas in the presence of human serum as a complement source with an LD₅₀ of 100 ng/ml. At this mAb concentration, fewer than 4% of more than 10⁵ available target sites were bound. Killing was not affected by changes in antigen expression observed during the cell cycle nor by loss of cell-surface targets via antigenic modulation. Cytotoxicity could be achieved with human serum diluted as low as 5%, suggesting that complement depletion in vivo should not limit activity. Autologous human serum could be used effectively as a complement source. The JD118 antigen target has not been identified, but it appears to be a glycoprotein. Up-regulation of antigen expression on normal B cells and chronic lymphocytic leukemia cells in vitro resulted in antigen-negative neoplasms becoming positive and thus targets for JD118 killing. The restricted expression, potent cytotoxic characteristics, and potential for up-regulation of its antigen make JD118 a possible candidate for ex vivo autologous bone marrow purging and in vivo therapeutic trials in patients with B cell neoplasms.This work was supported by ACS grants PRTF-135 and IM-551, the Michael and Ethel Cohen Fellowship Fund, and the Lucille P. Markey Trust. D. A. Scheinberg is a Lucille P. Markey Scholar Correspondence to: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA     

Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2

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The control of IgM expression in a murine B cell lymphoma

The regulation of IgM expression was studied in clones derived from a murine B lymphocyte cell line, WEHI279.1. During normal B cell development IgM heavy chain synthesis increases concomitantly with heightened IgM secretion and reduced cell-surface IgM. However, in these subclones, the levels of membrane-bound and secreted IgM were regulated independently of one another. The amount of IgM secreted by the cells was tightly coupled to the amount of heavy chain synthesis, suggesting that the major control of secretion is pretranslational. Surface IgM exhibited a more complex regulation, with both pre- and posttranslational components. Variation in the expression of both forms of IgM occurred at high frequency. Although IgM expression follows a unidirectional pathway in nontransformed cells, the variability in these tumor cells was reversible and cellautonomous. High levels of phenotypic variability may be important in the ability of transformed cells to escape the immune response.     

Analysis of effects induced by a pollock protein hydrolysate on early development, innate immunity and the bacterial community structure of first feeding of Atlantic halibut (Hippoglossus hippoglossus L.) larvae

A pollock protein hydrolysate was used for enrichment of the live feed offered to halibut larvae from the onset of exogenous feeding and the effects of treatment on selected innate immune parameters studied. The effects of treatment on the bacterial community structure of larvae were furthermore studied using the PCR–DGGE method. C3 and lysozyme were identified in larvae already at the onset of first feeding and low concentrations of IgM detected at this stage indicate maternal origin. Endogenous production of IgM was validated in the gastrointestinal tract of larvae from 29 days post onset of first feeding, with similar concentrations found in both groups. Feeding the peptide-enriched live feed stimulated production of lysozyme and affected the distribution of C3 in larval tissue but survival and normal development of halibut larvae were not affected by the treatment. Vibrio sp. and Pseudoalteromonas sp. dominated the bacterial community of larvae from both groups and peptide enrichment of the live feed was not found to affect the bacterial community structure associated with surface sterilized larvae.     

Human C4-binding protein: N-terminal amino acid sequence analysis and limited proteolysis by trypsin

Fres isolated blood cells recombined with normal heparinized plasma and then incubated with endotoxin, induced a 100-fold increase in monocyte tissue thromboplastin synthesis. In contrast, recombination of these cells with heat inactivated plasma, cobra venom factor-treated plasma, Ca²⁺-free plasma, or BioRex 70-treated plasma (plasma free of Clq and D) before incubation with endotoxin, failed to induce monocyte synthesis of tissue thromboplastin. These results strongly support the hypothesis that complement is required for endotoxin stimulation of blood monocyte synthesis of tissue thromboplastin.     

Age-related changes of immunoglobulin levels in African green monkeys (Cercopithecus aethiops)

Serum IgG, IgA, and IgM levels were measured in domestically bred African green monkeys (Cercopithecus aethiops) ranging in age from 0 day to 49 months as well as in adult (5 years or older) animals of wild origin. Transplacental transfer of IgG was observed. IgG, IgA, and IgM levels increased with increasing age except for a temporal decrease of IgG level in the first month of life.     

Herpes Simplex Virus-Specific IgM,IgA and IgG Subclass Antibody Responses in Primary and Nonprimary Genital Herpes Patients

To clarify the humoral immunity in herpes simplex virus (HSV) infection, HSV-specific IgM, IgA and IgG subclass antibody responses were studied in patients with genital herpes: 17 primary, 13 recurrent and 6 nonprimary first episode. A total of 181 serum samples serially collected from the patients, 5 per patient until 213 days after the onset of disease (on average), were analyzed by an enzyme-linked immunosorbent assay. IgGl, IgG3 and IgA were detected in all patients with primary and nonprimary infections, whereas IgG4 was detected in 74% of only those with nonprimary infections and IgG2 was detected in none. IgM was detected in 100% of the patients with primary infections, but also in 68% of those with nonprimary infections. IgA showed a peak similar to that of IgM in patients with primary infections. No significant difference was observed in the detection rate or pattern of antibody responses between the recurrent and nonprimary first episode infections, nor between the HSV-1 and HSV-2 infections. These findings may be useful to improve the diagnostic potential of HSV serology.