Evidence that intestinal IgA plasma cells in μ,ϰ transgenic mice are derived from B-1 (Ly-1 B) cells

Kroese, Frans G. M.; Ammerlaan, W.; Kantor, Aaron B.

doi:10.1093/intimm/5.10.1317

Cited by 70 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8), while peritoneal B-1 cells did as like intestinal B-1 cells. Further, peritoneal B-1 cells have been considered to be one of the major sources for intestinal IgA plasma cells (14,19,20,30). Taken together, these findings provide new evidence for the existence of a CMIS-independent IgA B cell development pathway and suggest for the first time that it consists of two distinct steps regulated by IL-15/IL-15R and IL-5/IL-5R signaling cascades.…”

Section: Discussionmentioning

confidence: 67%

“…As results, the sIgA ϩ B220 low fraction also expressed Mac-1, but not sIgA ϩ B220 high fraction (data not shown). Because Mac-1 expression has been shown to associate with B-1, but not B-2, subset (16,17,19,20), these results further indicate that sIgA ϩ B220 low and B220 high fractions belong to B-1 and B-2 cells, respectively. In vivo treatment with IL-15 resulted in the preferential increase of sIgA ϩ B-1 cells when compared with B-2 cells (Fig.…”

Section: Enhancement Of Siga ϩ B-1 Cells At Iga Effector Sites By In mentioning

confidence: 69%

“…FITC-conjugated anti-IgA (PharMingen, R5-140), PE-conjugated anti-CD45R/B220 (PharMingen, RA3-6B2), and biotinylated anti-IgM (PharMingen, AF6-78) followed by streptavidin-conjugated PerCP (Becton Dickinson, Sunnyvale, CA) were used for the separation of sIgM ϩ sIgA Ϫ or sIgA ϩ B-1 and B-2 cells for the analysis of IL-15R and C␣ expressions and IgA production (14, 16, 17, 28 -30). In some cases, appropriate fluorescence conjugated anti-Mac-1 mAb (PharMingen, M1/70) was also used for multicolor FACS separation of B-1 and B-2 cells (16,17,19,20). These samples were then subjected to flow cytometry analysis by using a FACScaliber (Becton Dickinson).…”

Section: Analysis and Purification Of B Cell Subsets By Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

Hiroi

Yanagita

Ohta

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-1 cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 mAb treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-1 cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-1 and B-2 cells were separated into surface (s)IgM+sIgA− and sIgM−sIgA+ fractions, IL-15R-specific mRNA was found to be predominant in both sIgM+sIgA− and sIgM−sIgA+ B-1 cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-1 and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-1 subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM+sIgA− B-1, but not sIgM+sIgA− B-2, cells were already class-switched cells because the germline Cα transcript was detected and was then further enhanced by IL-15. IL-15 also supported differentiation of both sIgM+sIgA− and sIgM−sIgA+ B-1 cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM+,IgA− and sIgM−sIgA+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues.

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Enhancement Of Siga ϩ B-1 Cells At Iga Effector Sites By In mentioning

confidence: 69%

Section: Analysis and Purification Of B Cell Subsets By Flow Cytometrymentioning

confidence: 99%

See 1 more Smart Citation

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

Hiroi

Yanagita

Ohta

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In normal individuals B-1 cells are responsible for the majority of nonimmune serum IgM and contribute substantial amounts of resting IgA (15)(16)(17)(18). B-1 cell-derived Ig generally adheres more closely to the germline state than B-2 Ig, as a result of diminished somatic mutation and reduced length of nontemplated N-insertions, and is thus repertoire restricted (19 -22).…”

mentioning

confidence: 99%

Cutting Edge Commentary: Two B-1 or Not To Be One

Rothstein

2002

The Journal of Immunology

View full text Add to dashboard Cite

B-1 cells differ from conventional B-2 cells both phenotypically and functionally. Two seemingly mutually exclusive hypotheses have been proposed to explain the origin of B-1 cells. The lineage hypothesis holds that certain B cell precursors are destined early on to become B-1 cells. The differentiation hypothesis holds that every B cell has the same potential to acquire B-1 characteristics. Reconsideration of previous studies of transgenic and knockout mice, plus recent results identifying differences between splenic and peritoneal B-1 cells, point to unexpected complexity in the pathway leading to B-1 status. A new paradigm is suggested, in which surface Ig signaling is required for B-1 cell production, but in which the signaling threshold and context that lead to B-1 cell development and/or expansion differ for particular B cell precursors. Surface Ig signaling may also produce receptor editing, apoptotic deletion, and tolerance induction; how these different outcomes are determined remains uncertain.

show abstract

“…In these mice, most B cells in the periphery bear the m and k transgenes but coexpression of variable proportions of intrinsic genes has also been described [8][9][10][11]. Spleen cells from transgenic animals were stimulated in vitro with LPS and fused with the non-secreting SP2/0 cell line.…”

Section: Introductionmentioning

confidence: 99%

Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation

1997

View full text Add to dashboard Cite

Fernández C, Alarcón-Riquelme ME, Sverremark E. Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation. Scand J Immunol 1997;45:240-247 In this work the authors tested the hypothesis that differential glycosylation may be one of the mechanisms by which B cells could be able to produce monospecific or polyreactive antibodies flexibly. The same genetic information will be used in both situations. To prove this hypothesis the authors used mice transgenic for the SP6 (m þ k) hybridoma cell line producing monoclonal antibodies (MoAbs) with specificity for the hapten 2,4,6-trinitrophenyl (TNP). In these animals most cells in the periphery express exclusively the transgene SP6. To obtain polyreactive antibodies (Abs) spleen cells from transgenic animals were stimulated in vitro with lipopolysaccharide (LPS). The authors used LPS derived B cell blasts to produce a hybridoma cell collection. A high proportion of the monoclonal antibodies were found to bind to TNP and to crossreact with unrelated antigens. Endogenous immunoglobulins (lgs) were not responsible for crossreactivity since the crossreactive clones only expressed the transgene products. This was demonstrated by polymerase chain reaction (PCR) amplification of cDNA and by sequencing analysis of the PCR products. The nucleotide sequences of the expressed mono-and crossreactive genes were identical to the sequences of the rearranged V H and V K SP6 which undoubtedly demonstrates that crossreactive Igs are derived from the same rearrangement and also that no mutations in the V H or V K or in the CDR3 could account for the observed crossreactivity. It is also shown here that the crossreactive antibodies bear the idiotype Id 20-5 characteristic of SP6 binding Abs. Crossreactive monoclonal antibodies were found to be slightly more glycosylated than the TNP-monospecific Abs. Furthermore, binding to TNP was not influenced by treatment with tunicamycin, an inhibitor of glycosylation, while, in the same molecule, other types of binding were considerably reduced. This supports the hypothesis of the importance of glycosylation in polyreactivity. INTRODUCTIONIt is estimated that 30-80% of non-selected natural antibodies (Abs) are polyreactive [1][2][3][4]. A high level of polyreactivity is found after polyclonal B cell activation with lipopolysaccharide (LPS) [2,3,5]. It is uncertain whether the polyreactive Abs induced after LPS stimulation are different from the Abs in the specific pool or if the polyreactive Abs are modified specific Abs.In the accompanying article [6], we have shown elsewhere that 2-4% of the monoclonal antibodies (MoAbs) originated after stimulation with LPS bound to the carbohydrate dextran B512 (Dx), and that the vast majority of them were crossreactive with the unrelated antigen bovine serum albumin (BSA). We also demonstrated that crossreactive Abs were more sensitive to deglycosylation promoted b...

show abstract

Evidence that intestinal IgA plasma cells in μ,ϰ transgenic mice are derived from B-1 (Ly-1 B) cells

Cited by 70 publications

References 0 publications

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

Cutting Edge Commentary: Two B-1 or Not To Be One

Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation

Contact Info

Product

Resources

About