Ontogeny of B lymphocyte function. VI. Ontogeny of thymus cell capacity to facilitate the functional maturation of B lymphocytes

Szewczuk, Myron R.; Sherr, David H.; Siskind, Gregory W.

doi:10.1002/eji.1830080514

Cited by 12 publications

(6 citation statements)

References 12 publications

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“…Studies using various inbred mouse strains have shown that the maturation of antibody avidity is regulated genetically and may vary between different individuals [17–19]. The cellular immune system, together with cytokines and the Th1/Th2 balance, may play an important role in this regulation and, for example, interferon‐gamma has been shown to augment avidity maturation [20–22]. High avidity antibodies are more effective in virus neutralization [23,24], which is important for immunity against enterovirus infections.…”

Section: Introductionmentioning

confidence: 99%

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

Heino

Lönnrot

Knip

et al. 2001

Clinical and Experimental Immunology

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SUMMARYEnterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

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Section: Introductionmentioning

confidence: 99%

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

Heino

Lönnrot

Knip

et al. 2001

Clinical and Experimental Immunology

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“…The absence of somatic mutation may relate to T cell dependence of the ontogeny of normal B cell functional maturation. Mouse B lymphocytes acquire the capacity to give a normal adult-like heterologous response between 7 and 10 d of age (32,33), and this functional maturation is independent of antigenic drive since it is observed in germ-free mice (34). In a model using irradiated mice, reconstituted with adult thymocytes and B cells from fetal liver and adult spleen, the maturation of B cells to produce antibodies with heterogenous affinities is shown to depend on cells derived from thymus.…”

Section: Discussionmentioning

confidence: 99%

Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.

Haire

Buell

Litman

et al. 1993

The Journal of Experimental Medicine

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SummaryImmunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human V. genes permitted identification of the germline V. genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human V. locus. The pattern of V. gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D/~ sequences also were identified, as was another sequence resulting from a unique recombination event linking J. to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline V~ genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM V. sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire. nalyses of the Ig repertoire, as represented in peripheral blood, have been the focus of recent investigations. Owing to the relative ease of PCR amplification, most of the efforts have been directed at the CDR3 junction and the generation of diversity through D. element (as well as J.) usage and modification (1-3). Studies of the human fetal and cord blood repertoires have been carried out using conventional cDNA libraries (4-7), and while the normal human V. repertoire has not been studied extensively in terms of expression of specific V. genes, recent advances in the enumeration and mapping of germline V. genes (8-10) now allow such investigations. These findings have had considerable impact in terms of our understanding of the developmental expression of Ig genes as well as the relationship of autoimmunity to specific genes. The nature of Ig gene usage in human primary immunodeficiency diseases, including X-linked agammaglobulinemia (11-13) common variable immunodeficiency (14) and severe combined immunodeficiency (15), has been examined. The present report addresses the Ig gene repertoire of patients with DiGeorge syndrome, a developmental field defect that involves dysmorphogenesis of the third and fourth pharyngeal pouches and is associated with varying degrees of fascial dysmorphia, hypoparathyroidism, anomalies of the great cardiac vessels, and partial development of the thymus. Abnormal B cell function in these patients is associated with the thymic ...

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“…It was further shown that immature B cells acquire the capacity to give a high-affinity PFC response only if adult thymus cells are given to the irradiated mice together with the immature B cells [20]. It was established that the thymus cell population acquires the capacity to facilitate maturation of the BCP between 7 and 10 days after birth [34]. Thus, maturation of the BCP appears to be regulated by maturation of the thymus.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of B lymphocyte function X. Strain differences in maturation of the capacity of the B lymphocyte population to produce a high‐affinity antibody response

et al. 1981

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The ontogeny of the B lymphocyte population to be capable of producing a highaffinity plaque-forming cell (PFC) response to a haptenic determinant was studied by cell-transfer techniques in five different mouse strains. Lethally irradiated adult mice were reconstituted with liver from fetal or neonatal donors or spleen from young donors as a source of B lymphocytes. In addition, all animals received 1 x 10' adult thymus cells. Recipients were immunized with dinitrophenylated bovine gammaglobulin (DNP-BGG) one day after cell transfer. The heterogeneity of affinity of their anti-DNP PFC response was assayed by hapten inhibition of plaque formation. It was established by use of congenic mice differing at the Igh locus that only donor cells responded under these conditions. By use of this transfer system, it was shown that the B cell populations of A/HeJ, AKR and C57L/J mice aquire the capacity to produce a high-affinity PFC response between day 15 and 18 of fetal life. The B cell populations of LAF, and DBA/l J mice mature between 7 and 10 days after birth. The B cell population of C 57 BL/6 J mice matures between 21 and 28 days of age. In LAFl and AKR mice, the B cell population acquires the capacity to generate a high-affinity indirect PFC response at approximately the same time as the capacity to generate a high-affinity direct PFC response. The time of maturation of the capacity to generate indirect PFC was found to differ in different strains of mice. Maturation of the capacity to produce indirect PFC appears to represent a dinstinctly different differentiation event from the acquisition of the capacity to produce a high-affinity PFC response. The data suggest that the maturation of the B cell population to be capable of producing high-affinity PFC is a precisely regulated differentiation event, the timing of which is strain-related. Preliminary data suggest that this regulation is not linked to either the H-2 haplotype or to the Igh allotype.

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Ontogeny of B lymphocyte function. VI. Ontogeny of thymus cell capacity to facilitate the functional maturation of B lymphocytes

Cited by 12 publications

References 12 publications

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.

Ontogeny of B lymphocyte function X. Strain differences in maturation of the capacity of the B lymphocyte population to produce a high‐affinity antibody response

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