B lymphocyte deficiency in IgH‐transgenic rabbits

Jasper, Paul; Rhee, Ki Jong; Kalis, Susan L.; Sethupathi, Periannan; Yam, Pi Chen; Zhai, Shi Kang; Knight, Katherine L.

doi:10.1002/eji.200737191

Cited by 7 publications

(7 citation statements)

References 47 publications

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“…Consequently, mature B cells were largely reduced in these mice. Similar observations have been reported for other Ig transgenic mice and rabbits [18,19]. However, Herzenberg et al failed to perform a detailed characterization of the B cell populations in their transgenic mice [18].…”

Section: Discussionsupporting

confidence: 68%

“…transgene prevented the transition from large (early) pre-B to small (late) pre-B cells [19]. In both examples, the transgenic animal lines were created with transgenes derived from the homologous species.…”

Section: Discussionmentioning

confidence: 99%

“…These genetic modifications created two IgH loci on different chromosomes. In addition to inhibition of rearrangements at the endogenous IgH loci, the expression of transgenic IgH genes has also been reported to cause severe B cell deficiency [18,19]. However, the mechanisms behind this phenomenon are unclear.…”

Section: Introductionmentioning

confidence: 99%

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Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin &Mgr; heavy-chain transgenic mice

Zhang¹,

Cheng²,

Chu³

et al. 2014

Front. Agr. Sci. Eng.

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In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro-and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and Vκ repertoire but exhibited an increased frequency of unique CDR3 in their Vλ repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgMexpressing B cells that expressed λ chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin &Mgr; heavy-chain transgenic mice

Zhang¹,

Cheng²,

Chu³

et al. 2014

Front. Agr. Sci. Eng.

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“…To localize transitional B cells in GALT during this process, we examined the appendix from an IgH transgenic (Tg) rabbit. These IgH Tg rabbits are deficient in B cells early in ontogeny, but IgM + B cells accumulate gradually first in the appendix and SR and later in PP, MLN, blood and spleen (30). The delayed temporal appearance of B cells in these rabbits offered an opportunity to study the early stages of peripheral B cell development.…”

Section: Resultsmentioning

confidence: 99%

Somatically Diversified and Proliferating Transitional B Cells: Implications for Peripheral B Cell Homeostasis

Yeramilli

Knight

2011

The Journal of Immunology

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The peripheral B cell compartment in mice and humans is maintained by continuous production of transitional B cells in the bone marrow (BM). In other species however, including rabbits, B lymphopoiesis in the BM abates early in life and it is unclear how the peripheral B cell compartment is maintained. We identified transitional B cells in rabbits and classified them into T1 (CD24hiCD21lo) and T2 (CD24hiCD21+) B cell subsets. By neutralizing BAFF in vivo, we found an arrest in peripheral B cell development at the T1 B cell stage. Surprisingly, T1 B cells were present in GALT, blood and spleen of adult rabbits, long after B lymphopoiesis was arrested. T1 B cells were distinct from their counterparts in other species because they are proliferating and the Ig genes are somatically diversified. We designate these newly described cells as T1d B cells and propose a model in which they develop in GALT, self-renew, and continuously differentiate into mature B cells, and thereby maintain peripheral B cell homeostasis in adults in the absence of B lymphopoiesis.

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“…Although our model has not yet been tested by interrupting chemokine-receptor interactions with neutralizing antibodies or chemical antagonists, our data suggest that B cells first home to the FAE after entering follicles, probably in response to FAE CCL20 expression. Jasper et al (34) reported evidence in IgH-transgenic rabbits similarly suggesting that B cells first home to the FAE. These rabbits carried a productive VDJ-Cμ transgene that unexpectedly blocked B cell development at the preB cell stage in the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Chemokine-Mediated B Cell Trafficking during Early Rabbit GALT Development

Zhai

Volgina

Sethupathi

et al. 2014

The Journal of Immunology

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Microbial and host cell interactions stimulate rabbit B cells to diversify the primary antibody repertoire in gut-associated lymphoid tissues (GALT). B cells at the base of appendix follicles begin proliferating and diversifying their V-(D)-J genes around 1 week of age, ∼5 days after B cells first begin entering appendix follicles, To gain insight into the microbial and host cell interactions that stimulate B cells to diversify the primary antibody repertoire, we analyzed B cell trafficking within follicles during the first week of life. We visualized B cells, as well as chemokines that mediate B cell homing in lymphoid tissues, by in situ hybridization, and examined B cell chemokine receptor expression by flow cytometry. We found that B cells were activated, and began downregulating their BCRs, well before a detectable B cell proliferative region appeared at the follicle base. The proliferative region was similar to germinal center dark zones, in that it exhibited elevated CXCL12 mRNA expression, and B cells that upregulated CXCR4 mRNA in response to signals acquired from select intestinal commensals localized in this region. Our results suggest that, after entering appendix follicles, B cells home sequentially to the FAE, the FDC network, the B cell:T cell boundary and, ultimately, the base of the follicle, where they enter a proliferative program and diversify the primary antibody repertoire.

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B lymphocyte deficiency in IgH‐transgenic rabbits

Cited by 7 publications

References 47 publications

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin &Mgr; heavy-chain transgenic mice

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin &Mgr; heavy-chain transgenic mice

Somatically Diversified and Proliferating Transitional B Cells: Implications for Peripheral B Cell Homeostasis

Chemokine-Mediated B Cell Trafficking during Early Rabbit GALT Development

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