A bird's eye view on human B cells

Weill, Jean‐Claude; Weller, Sandra; Reynaud, Claude‐Agnès

doi:10.1016/j.smim.2004.08.007

Cited by 28 publications

(43 citation statements)

References 28 publications

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“…Although replacement mutations do occur more frequently per codon in the CDR, this could be due to higher tolerance for changes in the regions not involved in main-chain folding. The mutations and the frequency of shark Ig mutants increase with age (24,33), and whether hypermutation acts as a contributor to the primary repertoire (36) or promotes affinity maturation in sharks is not clear; the mutants we observe might be the result of a combination of both.…”

Section: Somatic Mutation and Evolutionmentioning

confidence: 84%

Somatic Hypermutation and Junctional Diversification at Ig Heavy Chain Loci in the Nurse Shark

Malecek

Brandman

Brodsky

et al. 2005

The Journal of Immunology

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We estimate there are ∼15 IgM H chain loci in the nurse shark genome and have characterized one locus. It consists of one V, two D, and one J germline gene segments, and the constant (C) region can be distinguished from all of the others by a unique combination of restriction endonuclease sites in Cμ2. On the basis of these Cμ2 markers, 22 cDNA clones were selected from an epigonal organ cDNA library from the same individual; their C region sequences proved to be the same up to the polyadenylation site. With the identification of the corresponding germline gene segments, CDR3 from shark H chain rearrangements could be analyzed precisely, for the first time. Considerable diversity was generated by trimming and N addition at the three junctions and by varied recombination patterns of the two D gene segments. The cDNA sequences originated from independent rearrangements events, and most carried both single and contiguous substitutions. The 53 point mutations occurred with a bias for transition changes (53%), whereas the 78 tandem substitutions, mostly 2–4 bp long, do not (36%). The nature of the substitution patterns is the same as for mutants from six loci of two nurse shark L chain isotypes, showing that somatic hypermutation events are very similar at both H and L chain genes in this early vertebrate. The cis-regulatory elements targeting somatic hypermutation must have already existed in the ancestral Ig gene, before H and L chain divergence.

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Section: Somatic Mutation and Evolutionmentioning

confidence: 84%

Somatic Hypermutation and Junctional Diversification at Ig Heavy Chain Loci in the Nurse Shark

Malecek

Brandman

Brodsky

et al. 2005

The Journal of Immunology

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“…This contrasts with the supposition that children Ͻ2 years of age are unable to diversify their B cells via GC reactions due to an immature MZ (24). As highlighted recently (66), the fact that mutated IgM ϩ CD27 ϩ B cells are detected in young children cannot be considered as direct evidence supporting the idea that SHM in these cells occurred during prediversification of the B cell repertoire (24,45).…”

Section: Cd27mentioning

confidence: 86%

“…The major conclusions of these studies were that IgM ϩ CD27 ϩ B cells: 1) are generated independently of GC; 2) undergo SHM during generation of the preimmune repertoire; and 3) are exclusively involved in responses to T cellindependent (TI) Ag. Consequently, it was proposed that IgM ϩ CD27 ϩ B cells do not represent bona fide memory B cells (24,45). These studies have impacted on humoral immunology by questioning the use of SHM as a marker of memory and the dogma of how memory B cells are generated.…”

Section: Igm ϩ Memory B Cells-do They Exist?mentioning

confidence: 99%

“…These studies have impacted on humoral immunology by questioning the use of SHM as a marker of memory and the dogma of how memory B cells are generated. Furthermore, these conclusions have been rapidly embraced by sections of the immunological community (45,46) without considering alternative and equally valid interpretations of the function and origin of IgM ϩ CD27 ϩ B cells and the contribution of switched memory B cells to TI immune responses. Next, we will outline the data supporting the conclusions from these studies (23,24,44) and then provide alternative explanations favoring the possibility that IgM ϩ CD27 ϩ B cells are memory cells.…”

Section: Igm ϩ Memory B Cells-do They Exist?mentioning

confidence: 99%

“…1, b and c). Thus, the presence of mutated IgM ϩ CD27 ϩ B cells in individuals unable to form GC led to the conclusion that these cells are generated independently of GC and therefore are not memory B cells (23,24,45). Alternative scenarios.…”

Section: Cells Are Generated Independently Of Gc"mentioning

confidence: 99%

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Human IgM+CD27+ B Cells: Memory B Cells or “Memory” B Cells?

Tangye

Good

2007

The Journal of Immunology

215

200

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Memory B cells are generated in germinal centers (GC) and contribute to serological immunity by rapidly differentiating into plasma cells. Human memory B cells can be identified by the expression of CD27. These cells exhibit more rapid responses than naive (CD27−) B cells following stimulation in vitro, consistent with the heightened kinetics of secondary responses in vivo. CD27+ B cells express mutated Ig V region genes; however a significant proportion continue to express IgM, suggesting the existence of IgM+ memory B cells. The observation that mutated IgM+CD27+ B cells are generated in humans who cannot form GC led to the conclusions that these cells are generated independently of GC and thus are not memory cells and that they mediate responses to T cell-independent Ag. Although some studies support the idea that IgM+CD27+ B cells participate in T cell-independent responses, many others do not. In this review we will provide alternate interpretations of the biology of IgM+CD27+ B cells and propose that they are indeed memory cells.

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Human splenic marginal zone B cells lack expression of activation‐induced cytidine deaminase

et al. 2005

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It has been speculated that somatic hypermutation of rearranged immunoglobulin variable (V) region genes does not only take place in the germinal center (GC) microenvironment, but also in the marginal zone (MZ) of the spleen, and that human peripheral blood IgM-positive B cells with somatically mutated V region genes may derive from mutating MZ B cells. As somatic hypermutation is strictly dependent on the enzyme activation-induced cytidine deaminase (AID), we used an AID-specific monoclonal antibody that is suitable for immunohistochemical staining to analyze human splenic MZ cells for AID expression. Analysis of tissue sections from 29 spleens revealed only very rare MZ cells (approx. 0.05%) showing AID staining, whereas in 25 of the spleen samples strong AID staining of GC B cells was observed. Thus, there are virtually no AID-expressing MZ B cells, indicating that somatic hypermutation does not take place at a significant level in the MZ. Consequently, it appears unlikely that the somatically mutated IgM B cells are generated in the splenic MZ. Moreover, the lack of AID-positive MZ B cells questions the recent speculation that B cell chronic lymphocytic leukemias with mutated V genes are derived from mutating MZ B cells.

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A bird's eye view on human B cells

Cited by 28 publications

References 28 publications

Somatic Hypermutation and Junctional Diversification at Ig Heavy Chain Loci in the Nurse Shark

Somatic Hypermutation and Junctional Diversification at Ig Heavy Chain Loci in the Nurse Shark

Human IgM+CD27+ B Cells: Memory B Cells or “Memory” B Cells?

Human splenic marginal zone B cells lack expression of activation‐induced cytidine deaminase

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