A Novel Mechanism for B Cell Repertoire Maturation Based on Response by B Cell Precursors to Pre–B Receptor Assembly

Wasserman, Robert; Li, Y.-S.; Shinton, Susan A.; Carmack, Condie E.; Manser, Tim; Wiest, David L.; Hayakawa, Kyoko; Hardy, Richard R.

doi:10.1084/jem.187.2.259

Cited by 112 publications

(107 citation statements)

References 33 publications

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“…[9][10][11]38 However, we cannot exclude the possibility that these cells have been selected and correspond to intermediates between preBCR + and immature B cells, in which the expression of the ⌿L chain is downregulated and light chain gene rearrangements initiated. Cotransfection of ⌿L-positive proB cells with the corresponding vectors and search for cell surface expression of the preBCR, 38,39 would allow one to distinguish between these two possibilities.…”

Section: Discussionmentioning

confidence: 99%

Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

et al. 2000

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The expression of the surrogate light chain (⌿L) -made of the -like (or 5) and the VpreB proteins -is a B cell-specific maturation marker. Using an anti-human VpreB mAb (4G7), we recently identified in human normal bone marrows, proB and preB cells that express the ⌿H-⌿L proB (proBCR) and the -⌿L preB (preBCR) receptors, respectively. In the present study, FACS and biochemical analysis confirm the broad proB and preB reactivity of the 4G7 mAb that contrasts with the narrow specificity of other available anti-⌿L reagents for preB cells. This mAb was used to explore intracytoplasmic and cell surface expression of the VpreB protein on a series of 92 precursor B cell ALLs (from 40 child and 52 adult patients), in combination with 24 other mAbs. The major result concerns the identification within proB (or BI) and common (or BII) ALLs, of proBCR − and proBCR + ALLs that express the VpreB in the cytoplasm or at the cell surface, respectively. The percentage of ALLs within these two VpreB sub-groups differ considerably between the ALL origin. In the pediatric series, ALLs present in the majority a proBCR + phenotype whereas we observed a proBCR − phenotype for adult ALLs. Based on VpreB expression, and in combination with other published data, we propose a refined classification for precursor B cell ALLs. Leukemia (2000) 14, 2103-2111.

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Section: Discussionmentioning

confidence: 99%

Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

et al. 2000

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“…Hardy, for example, has proposed that the VDJ rearrangements that form good VpreB͞ 5 pre-BCR complexes and positively select B-2 cells are actually toxic to developing B-1 cells, which can only pass this developmental checkpoint if VpreB͞ 5 pre-BCR complex formation fails (23). This inherent mechanism would explain evidence presented earlier by Hardy's group (15), which showed clearly that the committed B-1 progenitors in fetal liver maintained their developmental commitment to the unique B-1 repertoire, even in adult adoptive recipients (15).…”

Section: Discussionmentioning

confidence: 99%

Phenotypically distinct B cell development pathways map to the three B cell lineages in the mouse

Tung

Mrazek

Yang

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

130

103

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B-1 cells ͉ B-2 cells ͉ CD138 ͉ MHC class II ͉ progenitors S ome time ago, our laboratory proposed the existence of three B lymphocyte lineages (B-1a, B-1b, and B-2) in the mouse (1-3). We based this proposal on in vivo reconstitution studies demonstrating that progenitors for these lineages are enriched differentially in traditional sites for lymphocyte progenitors, i.e., B-1a progenitors are found principally in fetal liver, neonatal spleen, and neonatal bone marrow (BM), whereas B-1b and B-2 progenitors are found principally in adult BM. In the ensuing years, alternate theories were advanced suggesting that antigendriven differentiation of mature B cells accounted for the development of these functionally distinct B cells subsets (4-9). However, in a recent paper, directly demonstrate that B-1a, B-1b, and B-2 belong to three separate lineages by showing that they derive from phenotypically and temporally distinct progenitors, i.e., progenitors for B-2 cells are phenotypically distinct from progenitors for B-1a and B-1b; among progenitors for B-1 cells, B-1a progenitors are found principally in neonates, whereas progenitors for B-1b are found principally in adults.Studies here provide key support for the existence of the distinct B cell lineages by showing that the predominant B cell development pathway in adults, where B-2 development predominates, is phenotypically distinct from the predominant pathway in neonates, where B-1 development predominates. In essence, we show that syndecan-1 (CD138) and MHC class II (I-A) are both expressed throughout B cell development in the predominant B cell pathway adult BM, beginning when Ig rearrangement is initiated [at Hardy fraction (Fr.) B (11)] and persisting thereafter (I-A), or terminating when the B cells reach maturity (CD138). In contrast, neither marker is expressed during early B cell development in the predominant pathway in neonatal BM and spleen, where I-A appears initially on mature B cells (12, 13), and CD138 is not detectable on most of the developing B cells.

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“…The ability of TSLP to drive the expansion of pre-BCRnegative precursors in the liver readily explains why mice transgenic for a heavy-chain gene that does not associate with 5 (48) are only able to efficiently generate transgenic B cells during the neonatal stage (49). Such cells are inefficiently produced later in life because, during adult lymphopoiesis, TSLP expands endogenous heavy-chain-expressing, pre-BCR-positive cells.…”

Section: Tslp Supports the Proliferation Of Adult Large Pre-b But Nomentioning

confidence: 99%

Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment

Vosshenrich

Cumano

Müller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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IL-7 and thymic stromal lymphopoietin (TSLP) are two major cytokines controlling murine B cell development. IL-7 has been studied extensively, but only recently has it become possible to unravel the role of TSLP in detail. We studied the biological activities of TSLP in B cell development at distinct ages in the mouse. On the one hand, TSLP is able to give rise to a measurable B1 cell compartment derived from fetal liver pro-B cells, although, as is the case for B2 cells, it does not play a prevalent role in the development of this subset. On the other hand, TSLP drives the proliferation of pro-B cells from the fetal and neonatal liver, but in the bone marrow environment, B cell precursors require pre-B cell receptor expression for TSLP responsiveness.

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A Novel Mechanism for B Cell Repertoire Maturation Based on Response by B Cell Precursors to Pre–B Receptor Assembly

Cited by 112 publications

References 33 publications

Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

Phenotypically distinct B cell development pathways map to the three B cell lineages in the mouse

Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment

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