Human Monoclonal Antibodies against Blood Group Antigens Preferentially Express a VH4‐21 Variable Region Gene‐Associated Epitope

Thompson, Keith M.; Sutherland, Janet; Barden, G.; Melamed, M.D.; Randen, Ingrid; Natvig, J. B.; Pascual, Virginia; Capraj, J. D.; Stevenson, Freda K.

doi:10.1111/j.1365-3083.1991.tb01574.x

Cited by 94 publications

(62 citation statements)

References 43 publications

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“…This member of the V H 4 gene family is extensively used for B cell Ag receptors with specificity for RBC and B lymphocyte carbohydrate Ags (65)(66)(67)(68)(69)(70). Ongoing studies will reveal whether similar patterns develop when mice are transplanted with adult human stem cells and this information may bear on the issue of what drives CD5 expression.…”

Section: Discussionmentioning

confidence: 99%

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Rossi

Medina

Garrett

et al. 2001

The Journal of Immunology

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Human B lineage lymphocyte precursors in chimeric nonobese diabetic/SCID mice transplanted with umbilical cord blood cells were directly compared with those present in normal bone marrow. All precursor subsets were represented and in nearly normal proportions. Cell cycle activity and population dynamics were investigated by staining for the Ki-67 nuclear Ag as well as by incorporation experiments using 5-bromo-2′-deoxyuridine. Again, this revealed that human B lymphopoiesis in chimeras parallels that in normal marrow with respect to replication and progression through the lineage. Moreover, sequencing of Ig gene rearrangement products showed that a diverse repertoire of VH genes was utilized by the newly formed lymphocytes but there was no evidence for somatic hypermutation. The newly formed B cells frequently acquired the CD5 Ag and had a short life span in the periphery. Thus, all molecular requirements for normal B lymphocyte formation are present in nonobese diabetic/SCID mice, but additional factors are needed for recruitment of B cells into a fully mature, long-lived pool. The model can now be exploited to learn about species restricted and conserved environmental cues for human B lymphocyte production.

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Section: Discussionmentioning

confidence: 99%

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Rossi

Medina

Garrett

et al. 2001

The Journal of Immunology

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“…Consequently, NAL-bearing self-antigens are widely available to engage 9G4 B cells both in soluble form and in the plasma membrane of RBC, lymphocytes, epithelial cells, tumor cells and apoptotic cells and indeed 9G4 antibodies have been shown to react with many of the antigens or cells described above ( [33,37,38,41,54,55,56,57,58,59,60] and our own observations that will be discussed below in more detail).…”

Section: G4 Antibodies In Health and Diseasementioning

confidence: 99%

Human innate B cells: a link between host defense and autoimmunity?

Milner

Anolik

Cappione

et al. 2005

Springer Semin Immun

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B cells play a variety of immunoregulatory roles through their antigen-presentation ability and through cytokine and chemokine production. Innate immune activation of B cells may play a beneficial role through the generation of natural cross-reactive antibodies, by maintaining B cell memory and by exercising immunomodulatory functions that may provide protection against autoimmunity. In this article, we review human B cell populations and their functional properties, with a particular focus on a population of inherently autoreactive B cells, which seem to play an important physiological role in innate immunity, but which, if selected into adaptive immune responses, appear to become pathogenic agents in systemic lupus erythematosus.

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“…However, the gene is used in response to immunization with blood group Rh antigens, mainly by those of IgM class [7]. It has also been found to encode antibodies against bacterial lipid A, again of IgM class [10,11].…”

Section: Introductionmentioning

confidence: 99%

Tracking of the V4–34 (VH4–21) gene in human tonsil reveals clonal isotype switch events and a highly variable degree of somatic hypermutation

Chapman

Mockridge

Hamblin

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThe V 4-34 (V H 4-21) gene has been found to encode certain IgM autoantibodies, and is mandatory for pathological IgM anti-erythrocyte antibodies of I/i specificity. The gene is also commonly used by normal IgM-positive B lymphocytes, but its involvement in B cells which have undergone class switching to IgG or IgA is less clear. In order to track V 4-34 gene usage and class switching events during a normal immune response, we have probed RNA in a limited area of human tonsil. Results indicate that the V 4-34 gene undergoes class switching to IgG or IgA, with the progeny either remaining unmutated or containing large numbers of somatic mutations. Mutational patterns indicate possible 'hot spots', and some mutations appear deleterious. At the level of individual B cells, we have tracked a clonal isotype switch event from IgM to IgA, with each retaining close to germ-line configuration. In addition, we have followed a clonal switch from a mutated IgM to IgG, with no further accumulation of somatic mutations. These data indicate that the V 4-34 gene is involved in a maturing immune response, and that the routes to production of IgG or IgA antibodies are various.

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Human Monoclonal Antibodies against Blood Group Antigens Preferentially Express a VH4‐21 Variable Region Gene‐Associated Epitope

Cited by 94 publications

References 43 publications

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Human innate B cells: a link between host defense and autoimmunity?

Tracking of the V4–34 (VH4–21) gene in human tonsil reveals clonal isotype switch events and a highly variable degree of somatic hypermutation

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