The bone marrow perisinusoidal niche for recirculating B cells and the positive selection of bone marrow‐derived B lymphocytes

Pillai, Shiv; Cariappa, Annaiah

doi:10.1038/icb.2008.89

Cited by 21 publications

(21 citation statements)

References 32 publications

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“…However, a growing body of evidence indicates that bone marrow also maintains a high level of immune responsiveness and demonstrates characteristics of a secondary lymphoid organ. 7,19,40 The marrow's highly vascularized architecture means that within minutes of IV injection, For personal use only. on May 10, 2018.…”

Section: Discussionmentioning

confidence: 99%

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

Moreau

Berger

Nelles

et al. 2015

Blood

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Key Points• Mouse inflammation models cause accumulation of B cells in the bone marrow within 12 hours and prior to peak emergency granulopoiesis.• Marrow B cells undergo spatial reorganization and are subjected to an altered cellular and secreted milieu.Systemic inflammation perturbs the bone marrow environment by evicting resident B cells and favoring granulopoiesis over lymphopoiesis. Despite these conditions, a subset of marrow B cell remains to become activated and produce potent acute immunoglobulin M (IgM) responses. This discrepancy is currently unresolved and a complete characterization of early perturbations in the B-cell niche has not been undertaken. Here, we show that within a few hours of challenging mice with adjuvant or cecal puncture, B cells accumulate in the bone marrow redistributed away from sinusoid vessels. This response correlates with enhanced sensitivity to CXC chemokine ligand 12 (CXCL12) but not CXCL13 or CC chemokine ligand 21. Concurrently, a number of B-cell survival and differentiation factors are elevated to produce a transiently supportive milieu. Disrupting homing dynamics with a CXC chemokine receptor 4 inhibitor reduced the formation of IgM-secreting cells. These data highlight the rapidity with which peripheral inflammation modifies the marrow compartment, and demonstrate that such modifications regulate acute IgM production within this organ. Furthermore, our study indicates that conversion to a state of emergency granulopoiesis is temporally delayed, allowing B cells opportunity to respond to antigen. (Blood. 2015;126(10):1184-1192

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Section: Discussionmentioning

confidence: 99%

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

Moreau

Berger

Nelles

et al. 2015

Blood

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“…The BM is well established as a primary lymphoid organ, but it also provides niches for B cells (25)(26)(27) and naive T cells (28) that, in situ, respond to blood-borne Ags. The BM is thus established as an important and unique secondary lymphoid organ.…”

Section: Discussionmentioning

confidence: 99%

Nonplasmacytoid, High IFN-α–Producing, Bone Marrow Dendritic Cells

O’Keeffe

Fancke

Suter

et al. 2012

The Journal of Immunology

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Plasmacytoid dendritic cells (pDC) are the producers of type I IFNs in response to TLR9 ligands. However, we have found that when bone marrow is depleted of pDC, the IFN-α produced in response to TLR9 ligands is not fully removed. We assign the source of this non-pDC IFN-α as a newly described DC type. It displays the high IFN-α producing activity of pDC but to a more limited range of viruses. Unlike pDC, the novel DC display high T cell stimulation capacity. Moreover, unlike mouse pDC, they are matured with GM-CSF and are less prone to apoptosis upon activation stimuli, including viruses. We propose that these DC constitute a novel bone marrow inflammatory DC type, ideally geared to linking innate and adaptive immune responses in bone marrow via their potent IFN-α production and high T cell stimulatory capacity.

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“…These sites are essential for interactions between antigen presenting cells, T cells, B cells and other accessory cells; cooperation between these cells results in an effective humoral immune response [20]. Although a primary lymphoid organ, the bone marrow may also serve as a secondary lymphoid organ [21], and also participate in the induction of humoral immune responses [22]. Circulation memory B cells and neutralizing antibodies provide the first line of defence against various pathogens [23].…”

Section: Introductionmentioning

confidence: 99%

Humoral responses and immune protection in mice immunized with irradiated T. gondii tachyzoites and challenged with three genetically distinct strains of T. gondii

et al. 2011

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Toxoplasma gondii is an obligate intracellular parasite that infects a variety of mammals and birds. T. gondii also causes human toxoplasmosis; although toxoplasmosis is generally a benign disease, ocular, congenital or reactivated disease is associated with high numbers of disabled people. Infection occurs orally through the ingestion of meat containing cysts or by the intake of food or water contaminated with oocysts. Although the immune system responds to acute infection and mediates the clearance of tachyzoites, parasite cysts persist for the lifetime of the host in tissues such as the eye, muscle, and CNS. However, T. gondii RH strain tachyzoites irradiated with 255Gy do not cause residual infection and induce the same immunity as a natural infection. To assess the humoral response in BALB/c and C57BL/6J mice immunized with irradiated tachyzoites either by oral gavage (p.o.) or intraperitoneal (i.p.) injection, we analyzed total and high-affinity IgG and IgA antibodies in the serum. High levels of antigen-specific IgG were detected in the serum of parenterally immunized mice, with lower levels in mice immunized via the oral route. However, most serum antibodies exhibited low affinity for antigen in both mice strain. We also found antigen specific IgA antibodies in the stools of the mice, especially in orally immunized BALB/c mice. Examination of bone marrow and spleen cells demonstrated that both groups of immunized mice clearly produced specific IgG, at levels comparable to chronic infection, suggesting the generation of IgG specific memory. Next, we challenged i.p. or p.o. immunized mice with cysts from ME49, VEG or P strains of T. gondii. Oral immunization resulted in partial protection as compared to challenged naive mice; these findings were more evident in highly pathogenic ME49 strain challenge. Additionally, we found that while mucosal IgA was important for protection against infection, antigen-specific IgG antibodies were involved with protection against disease and disease pathogenesis. Most antigen responsive cells in culture produced specific high-affinity IgG after immunization, diverse of the findings in serum IgG or from cells after infection, which produced low proportion of high-avidity IgG.

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The bone marrow perisinusoidal niche for recirculating B cells and the positive selection of bone marrow‐derived B lymphocytes

Cited by 21 publications

References 32 publications

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

Nonplasmacytoid, High IFN-α–Producing, Bone Marrow Dendritic Cells

Humoral responses and immune protection in mice immunized with irradiated T. gondii tachyzoites and challenged with three genetically distinct strains of T. gondii

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