Rapid Induction of Splenic and Peritoneal B-1a Cells in Adult Mice by Thymus-Independent Type-2 Antigen

Whitmore, Alan C.; Neely, Harold R.; Diz, Ramiro; Flood, Patrick M.

doi:10.4049/jimmunol.173.9.5406

Cited by 9 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FOB cells are implicated in T‐cell‐mediated immune responses. MZB cells and B1a B cells respond to T‐independent antigen 26 . Decreased FOB and increased MZB cells in aged B10.D2 mice have been reported previously 27 .…”

Section: Discussionsupporting

confidence: 51%

Intra‐bone marrow bone marrow transplantation rejuvenates the B‐cell lineage in aged mice

et al. 2009

View full text Add to dashboard Cite

Age-related reductions in the frequency and absolute number of early B lineage precursors in the bone marrow of aged mice have been reported. Reversal of B-cell lineage senescence has not been achieved. Age-related impairment of the B-cell lineage is caused by the decreasing functionality of hematopoietic and B lineage precursors, and reduced efficacy of bone marrow stromal cells that constitute the bone marrow microenvironment. To induce rejuvenation of aged B cells, we injected whole bone marrow from young donors to irradiated aged recipients through the tibia and analyzed B-cell development and immune responsiveness. In aged mice, we found significant reductions in the frequencies and absolute numbers of pro-B cells (B220 + CD43 + CD24 + BP-1 À and B220 + CD43 + CD24 int BP-1 + ) and pre-B cells (B220 + CD43 + CD24 high BP-1 + and B220 + CD43 À IgM À IgD À ). Intra-bone marrow bone marrow transplantation (IBM-BMT) of young marrow cells including both hematopoietic stem cells and bone marrow stromal cells reversed the reduction of pro-B cells and pre-B cells. In the periphery, the frequency and absolute number of marginal zone-B cell were not significantly different between young, old and IBM-BMT group. The frequency of follicular-B cells in the IBM-BMT group was significantly increased compared to old group. The frequency of B1a B cells in the peritoneal cavity was significantly decreased in the IBM-BMT group. Antibody production against T-independent antigens was not different among the young, the aged and IBM-BMT groups.

show abstract

Section: Discussionsupporting

confidence: 51%

Intra‐bone marrow bone marrow transplantation rejuvenates the B‐cell lineage in aged mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…IL-5Rα is constitutively expressed on B-1 cells (82–84) and is important to development, differentiation, and self-renewal of B-1 cells (85). Our data demonstrate that the PC-specific IgM produced in PD-L2 −/− mice is highly represented by the T15 Id, potentially identifying a unique clonal specificity through which PD-L2 exerts regulatory control, especially upon egress to the spleen, given the predilection of B-1 cells for the spleen for the purpose of Ab secretion (25, 45, 86–90). Notably, our work shows PC-specific B-1 cells constitutively express PD-L2 and work from others has shown depletion of PD-L2 + B-1 cells significantly decreases PC-specific IgM levels (26), thereby demonstrating the key role PD-L2 + PC-specific B-1 cells play in maintaining PC-specific Ab levels.…”

Section: Discussionmentioning

confidence: 86%

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5–Dependent Mechanism

McKay

Haro

Daly

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

B-1 cells produce natural antibodies which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural antibodies against phosphorylcholine (PC). Naïve PD-L2-deficient (PD-L2−/−) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2−/− mice with selectively enhanced protection against PC-expressing non-typeable Haemophilus influenzae (NTHi), but not PC-negative NTHi, relative to wild type mice. PD-L2−/− mice had significantly increased PC-specific CD138+ splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 idiotype. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naïve PD-L2−/− mice and irradiated chimeras reconstituted with PD-L2−/− B cells had significantly higher levels of IL-5 – a potent stimulator of B-1 cell Ab production. PDL2 mAb blockade of wild type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PDL2 mAb blockade significantly increased IL-5+ T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PDL2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis.

show abstract

“…1E and 5C). This long-term maintenance of peritoneal Ag-specific B-1b cells following immunization has not been observed (49) or examined (50, 51) in previous studies using BCR transgenic mouse strains to examine B cell expansion in response to purified TI-2 Ags, although it was reported for α-1,3 dextran specific B-1b cells in V H J558 Tg mice following Enterobacter cloacae challenge (16). Moreover, accumulation and maintenance of Ft-LPS-specific peritoneal B-1a cells 2 months following Ft-LPS immunization was reported by Cole et al (22).…”

Section: Discussionmentioning

confidence: 90%

Programmed Cell Death 1 Suppresses B-1b Cell Expansion and Long-Lived IgG Production in Response to T Cell-Independent Type 2 Antigens

Haas

2011

The Journal of Immunology

View full text Add to dashboard Cite

B1b cells play a key role in producing antibodies (Ab) against T cell-independent type 2 (TI-2) antigens (Ags). However, the factors regulating Ab production by this unique B cell subset are not well understood. In this study, a detailed analysis of the B cell response to TNP-Ficoll was performed using normal mice. TNP-Ficoll delivered i.p. or i.v. induced rapid Ag-specific B-1b cell activation, expansion, isotype switching and plasmablast/plasma cell differentiation. Ag-specific B-1b cell numbers peaked at day 5 and then gradually declined in the spleen but remained elevated in the peritoneal cavity beyond 40 days post-immunization. In addition to expressing CD43, CD44, and CD86, Ag-activated B-1b cells transiently expressed PD-1, which functionally suppressed BCR-induced B-1b cell in vitro proliferation when additional costimulatory signals were lacking. Inhibiting PD-1:PD-1 ligand (PDL) interactions during TNP-Ficoll immunization significantly enhanced Ag-specific B-1b cell expansion and the frequency of IgG isotype switching and plasmablast/plasma cell differentiation. Remarkably, PD-1 mAb blockade during the first week following immunization resulted in significantly increased numbers of both splenic and bone marrow Ag-specific IgG3, but not IgM, secreting cells at both early (day 5) and late (week 6) timepoints. Moreover, Ag-specific serum IgG3, as well as IgG2c, IgG2b, and IgA levels remained significantly elevated in PD-1 mAb-treated relative to control Ab-treated mice for at least 6 weeks post-immunization. Thus, PD-1:PDL interactions occurring shortly after initial TI-2 Ag encounter play a critical role in suppressing Ag-specific B-1b cell expansion and the development of long-term IgG-producing bone marrow and spleen cells.

show abstract

Rapid Induction of Splenic and Peritoneal B-1a Cells in Adult Mice by Thymus-Independent Type-2 Antigen

Cited by 9 publications

References 55 publications

Intra‐bone marrow bone marrow transplantation rejuvenates the B‐cell lineage in aged mice

Intra‐bone marrow bone marrow transplantation rejuvenates the B‐cell lineage in aged mice

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5–Dependent Mechanism

Programmed Cell Death 1 Suppresses B-1b Cell Expansion and Long-Lived IgG Production in Response to T Cell-Independent Type 2 Antigens

Contact Info

Product

Resources

About