Patterned acquisition of the antibody repertoire: diversity of the hemagglutinin-specific B-cell repertoire in neonatal BALB/c mice.

Cancro, Michael P.; Wylie, Dwane E.; Gerhard, Walter; Klinman, Norman R.

doi:10.1073/pnas.76.12.6577

Cited by 61 publications

(39 citation statements)

References 21 publications

(19 reference statements)

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“…It is possible that the only selective pressure on V region genes is the maintenance of a minimal V gene pool and the Igh-V locus may be permissive to a wide variety of evolutionary changes in size, composition, or organization. On the other hand, certain, as yet unrecognized, features of V gene organization may be important in the development of the antigen specific receptor repertoire, for example, the developmental read-out of particular V genes (55,56) or antigen specificities (57,58) . 56), who found that 7 of 9 fetal liver hybridomas express the VH7183 family.…”

Section: Resultsmentioning

confidence: 99%

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Brodeur¹,

Osman²,

Mackle³

et al. 1988

The Journal of Experimental Medicine

108

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Studies ofIg gene structure and organization during the past decade have illuminated the central mechanisms of antibody diversification: the somatic rearrangement and reassortment of multiple gene segments, junctional flexibility, and point mutation . The inherited set of Ig gene segments provides a diversified genetic basis upon which these dynamic processes operate during ontogeny. Thus, the composition of these germline genes imposes a major influence on the development of the antibody repertoire.The present study examines the germline content and organization of the mouse heavy chain variable region genes (V genes) . We set out to analyze the locus in sufficient detail and resolution to provide the basis for determining the extent of inherited Vgene diversity, the evolution ofthe germline repertoire, and any functional consequences of the physical arrangement of the V gene segments .The mouse Igh locus consists of at least 100-200 V genes (1-3). V gene families, defined by nucleotide sequence relationships, comprise distinct sets of highly related V genes that can be identified by hybridization using prototypic V gene probes . This classification of V gene families (l, 4) has provided a useful framework for the study of germline V gene content, polymorphism, and utilization (1-7). Whereas the general organization of the Igh locus is 5'-V HDJ .-C -3' (8, 9), previous studies of V gene family organization have resulted in partial, relatively low resolution maps lacking consistency between reports (10-12)."Deletion mapping" takes advantage of the fact that V, gene rearrangements result in the deletion of DNA originally separating the rearranged V gene segment and the DJ .-CH region (13). We have constructed a panel of 32 pre-B cell lines, most of which have rearranged V, genes on both chromosomes. Since these cell lines were derived from Fi mice heterozygous at the Igh locus, V, gene deletions can be identified using RFLPs. V, gene analyses of 51 independently rearranged chromosomes are consistent with a single V, gene map order of nine V, gene families. The genomic stability of these cell lines and consistent deletion profiles of all 51 rearranged loci provide a high resolution V gene map that has compelling experimental support.

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Section: Resultsmentioning

confidence: 99%

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Brodeur¹,

Osman²,

Mackle³

et al. 1988

The Journal of Experimental Medicine

108

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“…Among the most striking features of the immune mechanism is the extraordinary reproducibility of repertoire expression (19)(20)(21)(22)(23)(24). Thus, in spite of the extremely complex mechanisms available for diversification and clonotype selection, repertoire sharing appears to be the rule among genetically identical individuals.…”

mentioning

confidence: 99%

“…Thus, in spite of the extremely complex mechanisms available for diversification and clonotype selection, repertoire sharing appears to be the rule among genetically identical individuals. This is particularly true in situations where the repertoire is limited such as in genetically identical frogs (19), bursectomized chickens (20), and, most importantly, neonatal mice (21)(22)(23)(24). Additionally, where it has been possible to evaluate the expression of clonotypes that occur in high frequency, or even rare clonotypes that are idiotypically identifiable, adult mice of the same strain apparently share repertoire (25)(26)(27)(28)(29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

Genetic and temporal control of neonatal antibody expression.

Denis¹

1983

The Journal of Experimental Medicine

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Two hybridoma cell lines were established with B cells derived from neonatal BALB/c spleen cells. The anti-dinitrophenyl (DNP) antibodies derived from these lines were characterized with respect to their isotype, affinity, and isoelectric point. Antiidiotypic reagents were prepared that permit an analysis of the representation of antibodies sharing idiotype with these two hybridomas in the developing and mature B cell pool of BALB/c mice (Igha) and other murine strains. One of the two antibodies, TF2-36, was found to be indistinguishable from 14% of anti-DNP monoclonal antibodies derived in fragment culture from spleen cells of 1-4-d-old BALB/c donors. B cells expressing this idiotype were found to represent approximately 2% of the anti-DNP-specific repertoire after the 1st wk of neonatal development and into adulthood. The second hybridoma antibody, TF2-76, was found to be expressed at very low levels during the first several days of neonatal development; however, B cells expressing this idiotype increased in frequency during the 2nd wk of neonatal development representing 7% of all DNP-responsive B cells 12-13 d after birth. The proportion of B cells expressing this idiotype also decreased to approximately 2% in adults. The relatively late appearance of B cells bearing this idiotype was confirmed by their susceptibility to tolerance induction after the 1st wk of neonatal development. Both the early neonatal clonotype, TF2-36, and the late neonatal antibody clonotype, TF2-76, were found to be expressed in a similar fashion in F1 mice constructed between Igha and Ighb parentals, but both were expressed at very low levels during the development of Ighb mice. Thus, the control of the magnitude of expression of these neonatal clonotypes appears to be associated with the Igh locus.

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“…In contrast, low doses of antigens would lead to an exclusive loading of pAPC. Thus, this quantitative model explains the observations that neonatal tolerance can be avoided by immunization with low amounts of antigens (8,15,19,45,49) or with pAPC bearing the antigen (20).…”

Section: Quantitative Differences Between the Immune Systems Of Neonamentioning

confidence: 99%

“…Second, the reactivity analysis of clonotypes obtained from mice immunized as adults or newborns with pHA, showed that in contrast to mice immunized as neoantes, those inoculated as adults displayed more frequent cross-reactive clonotypes (data not shown). These differences can be accounted for by the particular T cell responsiveness of neonates and by the more restricted B cell repertoire of the young mice (45).…”

Section: Humoral Responses Of Mice Immunized As Neonates With Naked Dnamentioning

confidence: 99%

Immune response of neonates elicited by somatic transgene vaccination with naked DNA

Bona¹

1997

Front Biosci

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Patterned acquisition of the antibody repertoire: diversity of the hemagglutinin-specific B-cell repertoire in neonatal BALB/c mice.

Abstract: The B-cell response of 12-to 14-

Cited by 61 publications

References 21 publications

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Genetic and temporal control of neonatal antibody expression.

Immune response of neonates elicited by somatic transgene vaccination with naked DNA

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