B‐cell subsets and the mature ­preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”

Martin, Flavius; Kearney, John F.

doi:10.1111/j.1600-065x.2000.imr017515.x

Cited by 341 publications

(224 citation statements)

References 70 publications

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“…Our findings also confirm and extend previous observations that selection of B cells into the various compartments of the spleen can be influenced by V usage [17][18][19]. Collectively, these observations support the hypothesis that entry to the various peripheral B cell compartments is influenced by ligand selection [17,18,20,21] and further suggest that selective pressure may be exerted at the level of categories of antigenic epitopes. V H usage in the bone marrow mature B cell subset was highly similar to that observed in progenitor immature B cells, but differs from that observed in all of the splenic subsets that we examined, including the transitional T1 population.…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, the shorter lengths of these MZ CDR-H3 also reflect increased exonucleolytic nibbling and altered use of shorter J H gene segments. Although it is possible that these are features of an as yet unrecognized bone marrow progenitor pool, there is a reasonable likelihood that they are a manifestation of ligand selection for a specific set of antigen binding site paratopes, and that this selection process could serve as a motive force for entry into the marginal zone [17,18,20,21].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, based on surface phenotypic criteria, the MZ subset appears to be enriched for cells that exist in a semi-activated state. Although given the proper stimuli MZ can engage in T-dependent responses, a large proportion of this population includes cells that appear primed to respond to T cell-independent challenges, such as those provided by polysaccharides on the surface of encapsulated bacteria [21,25,26]. The question then arises whether correlations can be made between the enrichment for short, polar CDR-H3 in the marginal zone and either the likelihood of pre-activation, or an altered range of preferred epitopes, or both.…”

Section: Discussionmentioning

confidence: 99%

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Categorical selection of the antibody repertoire in splenic B cells

et al. 2007

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In the bone marrow, the passage of developing B cells through critical checkpoints of differentiation is associated with a reduction of specific categories of CDR3 of the Ig heavy chain (CDR-H3), particularly those with excessive hydrophobic or charged amino acids and those with a length of eight or fewer residues. To gain insight into the role of CDR-H3 content in the development of B cells in the spleen, we compared the sequences of V H 7183DJCl transcripts from sorted transitional T1, marginal zone, and follicular B cell subsets to those expressed by immature IgM + IgD -and mature IgM lo IgD hi B cells in the bone marrow. Although differences in V H utilization were noted, the T1 CDR-H3 repertoire showed extensive similarity to that of immature bone marrow B cells, and the follicular CDR-H3 repertoire most resembled that of mature bone marrow B cells. Unlike the splenic follicular and bone marrow mature B cell CDR-H3 repertoires, the marginal zone B cell CDR-H3 repertoire retained both short and highly charged amino acid motifs, including those with two arginines. Our findings suggest that antigen binding sites containing specific categories of CDR-H3 sequence content may inhibit, permit, or even facilitate passage of the host B cell through critical checkpoints in peripheral as well as central development.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Categorical selection of the antibody repertoire in splenic B cells

et al. 2007

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“…These two B-cell subsets are producers of natural IgM and they also rapidly produce neutralizing Ab against blood-borne bacterial and viral pathogens at early stage of infection [13,25]. Our previous studies show that class A SR-deficient mice have defects in the local clearance function in the spleen and display increased levels of serum natural IgM [10,11].…”

Section: Class a Sr Deficiency Results In Increased Production Of Thementioning

confidence: 99%

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

et al. 2010

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Recognition of microbial components by TLR, key sensors of infection, leads to induction of inflammatory responses. We found that, in vivo, TLR4 engagement by LPS induces upregulation of the class A scavenger receptors (SR) macrophage receptor with a collagenous structure (MARCO) and SR-A, which occurs, at least in the case of MARCO, via both MyD88-dependent and -independent pathways. When challenging mice with a low dose of LPS followed by a high dose, class A SR-deficient mice showed a higher survival rate than WT mice. This was paired with increased production of IL-10 and anti-LPS Ab, as well as increased activation status of marginal zone B cells. However, the receptors were not crucial for survival when challenging mice i.p. with Neisseria meningitidis or Listeria monocytogenes, but they were found to contribute to microbial capture and clearance. This indicates physiological significance for the up-regulation of class A SR during early stages of bacterial infection. Thus, we believe that we have revealed a mechanism where SR regulate the activation status of the immune system and are involved in balancing a proper immune response to infection. This regulation could also be important in maintaining tolerance since these receptors have been shown to be involved in regulation of self-reactivity.Key words: Class A scavenger receptors . KO mice . LPS response . Spleen marginal zone B cells IntroductionLPS is a cell wall component of gram-negative bacteria, recognized, amongst others, by the TLR4/MD2 signalling receptor complex. Animals that have mutations in MD2 or TLR4 are susceptible to gram-negative bacterial infection due to the failure to sense LPS [1,2]. However, when animals sense LPS and respond too vigorously, they may be the victims of their own inflammatory overreaction. Therefore, the outcome of bacterial infection is determined not only by the ability to sense endotoxin, but also by mechanisms limiting the inflammatory response. Accordingly, mammals are equipped with many LPS detoxification mechanisms preventing vigorous inflammation [3]. For example, soluble proteins, such as natural Ab-binding LPS, prevent it from engaging the TLR4/MD2-complex and protect animals from endotoxin challenge [4,5]. Further, LPS can be Ã These authors contributed equally to this work. Class A SR MARCO (macrophage receptor with a collagenous structure) and SR-A (scavenger receptor A) have a potential for this type of regulation, since their ligand repertoire includes LPS and they are expressed by macrophages that respond quickly to infection. MARCO has a restricted expression pattern being expressed on specific macrophage subsets in spleen marginal zone (MZ), lymph nodes and peritoneum, whereas SR-A is more widely expressed. In vitro studies have shown that the expression of both receptors can be up-regulated in a TLR-dependent manner, suggesting that they might play a regulatory role in TLRmediated innate immune response [7,8].Being expressed primarily on MZ macrophages in the naïve spleen, MARCO and SR-A are in clos...

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“…Many studies have explored the key aspects of MZ B‐cell generation 8, 9, 10, 11. The B‐cell receptor (BCR) has been reported as important in the development from immature B cells into mature FO or MZ B cells 7.…”

Section: Introductionmentioning

confidence: 99%

CD19 regulates ADAM28‐mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells

Zhu

Xiao²,

Liu³

et al. 2017

J Cellular Molecular Medi

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As the first line of defence, marginal zone (MZ) B cells play principal roles in clearing blood‐borne pathogens during infection and are over‐primed in autoimmune diseases. However, the basic mechanisms underlying MZ B‐cell development are still unclear. We found here that CD19 deficiency blocked the differentiation of marginal zone precursors (MZP) to MZ B cells, whereas CD19 expression in CD19‐deficient MZP rescues MZ B‐cell generation. Furthermore, CD19 regulates Notch2 cleavage by up‐regulating ADAM28 expression in MZP. Finally, we found that CD19 suppressed Foxo1 expression to promote ADAM28 expression in MZP. These results suggest that CD19 controls the differentiation of MZP to MZ B cells by regulating ADAM28‐mediated Notch2 cleavage. Thus, we demonstrated the basic mechanisms underlying the differentiation of MZP to MZ B cells.

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B‐cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”

Cited by 341 publications

References 70 publications

Categorical selection of the antibody repertoire in splenic B cells

Categorical selection of the antibody repertoire in splenic B cells

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

CD19 regulates ADAM28‐mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells

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B‐cell subsets and the mature ­preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”

Cited by 341 publications

References 70 publications

Categorical selection of the antibody repertoire in splenic B cells

Categorical selection of the antibody repertoire in splenic B cells

A regulatory role for macrophage class A scavenger receptors in TLR4‐mediated LPS responses

CD19 regulates ADAM28‐mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells

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B‐cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”