Effects of Anti‐Ig Antibodies on the Development and Differentiation of B Cells

Cooper, Max D.; Kearney, John F.; Gathings, William E.; Lawton, Alexander R.

doi:10.1111/j.1600-065x.1980.tb00329.x

Cited by 100 publications

(42 citation statements)

References 93 publications

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“…In pre-B-cell lines an increase in free intracellular Ca2+ can be demonstrated after cross-linkage of the ,/ai LC receptors (28,37) but the signaling pattern more closely resembles that of newly formed B cells than mature B cells in that the inositol phospholipid hydrolysis pathway is engaged only in the mature B cell (39). Signaling through the surface IgM receptors on immature B cells in fact leads to clonal abortion rather than the activation response that characterizes mature B cells (39,40). These observations suggest that pre-B cells may receive a negative signal via their pu/a LC receptors.…”

Section: Discussionmentioning

confidence: 85%

Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

Nishimoto

Kubagawa

Ohno

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

100

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Early experimental observations contrary to this concept of pre-B-cell development (6-10) have received unexpected support from the recent discovery of A5 and Vpre-B genes in mice (11-13) and their counterparts in humans (13-16). The Vpre-B gene has significant homology to the LC variable region (VL) genes but lacks recombination signal sequences (12). The A5 gene encodes a protein containing LC joining region (JL)-and A-chain constant region (CA)-like sequences (13,15,16). These A-locus genes are also unusual in that they do not require rearrangement for their expression, which occurs exclusively in pre-B cells (11)(12)(13)(14)(15)(16). The Vpre-B and A5 gene products can be identified together with ,t chains on murine (17) and human (13, 15, 18) pre-B-cell lines. The A5 product of =22 kDa is covalently attached to membranebound ,L chains, while the 18-kDa Vpre-B protein is noncovalently bound (13,17,18

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Section: Discussionmentioning

confidence: 85%

Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

Nishimoto

Kubagawa

Ohno

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

100

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“…Crosslinking of the B cell receptor (BCR) in the absence of additional costimulatory signals can lead to B cell apoptosis (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Apoptotic depletion of B cells through BCR crosslinking has been extensively described for immature B cells as a mechanism by which autoreactive B cells are removed from the B cell repertoire.…”

Section: Introductionmentioning

confidence: 99%

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Brightbill¹,

Jeet²,

Lin³

et al. 2010

J. Clin. Invest.

100

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IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1′ domain, and using genetically modified mice that contain the human M1′ domain inserted into the mouse IgE locus, we demonstrated that M1′-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1′-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1′-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1′-specific antibodies may be a novel treatment for asthma and allergy.

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“…Because of the potential side effects of injection of large quantities of xenogenic Ab (15), these studies did not provide conclusive results. Chronic anti-Ab treatment involves delivery of an extraordinary amount of Ab, which may alter the microenvironment and concomitant cell-cell interactions that occur during infection with T. gondii (15)(16)(17). In addition, despite the extraordinary amount of Ab used, the anti-Ab may not completely deplete B cell populations in vivo, and although serum IgM is reduced to undetectable levels, IgG is generally readily detectable, albeit at levels 10-to 1000-fold lower than normal (17).…”

mentioning

confidence: 99%

“…Chronic anti-Ab treatment involves delivery of an extraordinary amount of Ab, which may alter the microenvironment and concomitant cell-cell interactions that occur during infection with T. gondii (15)(16)(17). In addition, despite the extraordinary amount of Ab used, the anti-Ab may not completely deplete B cell populations in vivo, and although serum IgM is reduced to undetectable levels, IgG is generally readily detectable, albeit at levels 10-to 1000-fold lower than normal (17). To elucidate whether B cells play a protective role in resistance against infection with T. gondii, additional studies using alternative approaches to deplete B lymphocytes are needed.…”

mentioning

confidence: 99%

Decreased Resistance of B Cell-Deficient Mice to Infection with Toxoplasma gondii Despite Unimpaired Expression of IFN-γ, TNF-α, and Inducible Nitric Oxide Synthase

Kang

Remington

Suzuki

2000

The Journal of Immunology

222

134

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The role of B cells in resistance against Toxoplasma gondii was studied using B cell-deficient (μMT) mice. Following peroral infection with 10 cysts of the ME49 strain, all μMT mice survived the acute stage of the infection but died between 3 and 4 wk after infection. In contrast, all control mice were alive at 8 wk after infection. At the stage during which μMT animals succumbed to the infection, parasite replication and pathology were most evident in their brains; small numbers of tachyzoites were also detectable in their lungs. Significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of μMT than in control mice. Large areas of necrosis associated with numerous tachyzoites were observed only in brains of μMT mice. Anti-T. gondii IgG Abs were detected only in sera of control mice, whereas similar levels of IFN-γ were detected in sera of both strains of mice. Amounts of mRNA for IFN-γ, IL-10, and inducible NO synthase in the brain did not differ between infected μMT and control mice. Expression of mRNA for TNF-α was increased in brains of μMT mice. Administration of polyclonal rabbit anti-T. gondii IgG Ab prevented early mortality and pathology associated with tachyzoites in the brain in the infected μMT mice. These results indicate that B cells play an important role, most likely through their production of specific Abs, in resistance to persistent active (tachyzoite) infection with T. gondii in mice, especially in the brain and lung.

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Effects of Anti‐Ig Antibodies on the Development and Differentiation of B Cells

Cited by 100 publications

References 93 publications

Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins.

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Decreased Resistance of B Cell-Deficient Mice to Infection with Toxoplasma gondii Despite Unimpaired Expression of IFN-γ, TNF-α, and Inducible Nitric Oxide Synthase

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