Differential impact of Toll-like receptor signaling on distinct B cell subpopulations

Meyer‐Bahlburg, Almut; Rawlings, David J.

doi:10.2741/4000

Cited by 32 publications

(28 citation statements)

References 121 publications

(185 reference statements)

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“…As expected, CD23 + B cells cultured with BLyS alone secreted minimal antibody, however, both TR and FO subsets secreted 10-fold more antibody following stimulation with either ODN 1826 plus anti-μ or STIC9 plus BLyS (Table 1 and Figure 4A, upper panel). Supernatants from MZ B cells revealed a similar pattern of Ig secretion, albeit at a greater magnitude, consistent with their vigorous response to TLR stimuli and propensity to undergo rapid plasma cell differentiation (56). Moreover, enzyme-linked immunosorbent spot (ELISPOT) analyses confirmed that ODN 1826 plus anti-μ or STIC9 plus BLyS induced antibody-secreting cell (ASC) formation ( Figure 4A, lower panel).…”

Section: Cd11csupporting

confidence: 49%

A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens

Sindhava

Oropallo

Moody

et al. 2017

Journal of Clinical Investigation

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Section: Cd11csupporting

confidence: 49%

A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens

Sindhava

Oropallo

Moody

et al. 2017

Journal of Clinical Investigation

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“…It is notable that expansion of a MZ-like B cell population was also observed in male BXSB mice bearing the trinitrophenyl/ ssDNA/ dsDNA-reactive Sp6 Ig Tg, irrespective of the presence of yaa [30]. Abnormal expansion or biology of murine MZ B cells, major autoIg producers [45] known to respond robustly to TLR ligands [46], has been linked to disease in some models [47–54]. Of note, the hyperproliferation of our BXSB Tg B cells to B cell receptor crosslinking is unusual for MZ B cells, which normally undergo apoptosis in response to this stimulus [46].…”

Section: Discussionmentioning

confidence: 99%

Regulation of basement membrane-reactive B cells in BXSB, (NZBxNZW)F1, NZB, and MRL/lpr lupus mice

et al. 2013

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Autoantibodies to diverse antigens escape regulation in systemic lupus erythematosus under the influence of a multitude of predisposing genes. To gain insight into the differential impact of diverse genetic backgrounds on tolerance mechanisms controlling autoantibody production in lupus, we established a single lupus-derived nephritis associated anti-basement membrane Ig transgene on each of four inbred murine lupus strains, including BXSB, (NZBxNZW)F1, NZB, and MRL/lpr, as approved by the Duke University and the Durham Veterans Affairs Medical Centers’ Animal Care and Use Committees. In nonautoimmune C57BL/6 mice, B cells bearing this anti-laminin Ig transgene are stringently regulated by central deletion, editing, and anergy. Here, we show that tolerance is generally intact in unmanipulated Ig transgenic BXSB, (NZBxNZW)F1, and NZB mice, based on absence of serum transgenic anti-laminin autoantibodies and failure to recover spontaneous anti-laminin monoclonal antibodies. Four- to six-fold depletion of splenic B cells in transgenic mice of these strains, as well as in MRL/lpr transgenic mice, and reduced frequency of IgM+ bone marrow B cells suggest that central deletion is grossly intact. Nonetheless the four strains demonstrate distinct transgenic B cell phenotypes, including endotoxin-stimulated production of anti-laminin antibodies by B cells from transgenic NZB mice, and in vitro hyperproliferation of both endotoxin- and BCR-stimulated B cells from transgenic BXSB mice, which are shown to have an enrichment of CD21-high marginal zone cells. Rare anti-laminin transgenic B cells spontaneously escape tolerance in MRL/lpr mice. Further study of the mechanisms underlying these strain-specific B cell fates will provide insight into genetic modification of humoral autoimmunity in lupus.

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“…There are several possible explanations for this. In mice naïve and memory B cells express TLRs, hence the systemic dissemination of bacteria and bacterial products in sepsis can lead to their antigen-independent polyclonal activation [45 -48]. First, memory B cells, located primarily in the splenic marginal zone, may be re-activated [38,39].…”

Section: Resultsmentioning

confidence: 99%

Experimental Sepsis Impairs Humoral Memory in Mice

et al. 2013

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Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool’s development, which is not complete 8 weeks after secondary immunization.

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Differential impact of Toll-like receptor signaling on distinct B cell subpopulations

Cited by 32 publications

References 121 publications

A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens

A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens

Regulation of basement membrane-reactive B cells in BXSB, (NZBxNZW)F1, NZB, and MRL/lpr lupus mice

Experimental Sepsis Impairs Humoral Memory in Mice

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