Thymus-independent type 2 antigen induces a long-term IgG-related network memory

Lange, Hans; Zemlin, Michael; Tănasă, Radu Iulian; Trad, Ahmad; Weiß, Thomas; Menning, Hauke; Lemke, Hilmar

doi:10.1016/j.molimm.2008.01.020

Cited by 6 publications

(17 citation statements)

References 64 publications

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“…Study of the molecular events during immune maturation of the TD anti-phOx response classically focused on analysis of mAb (9, 13, 14) secreted by hybridomas produced by fusion of permanently growing myeloma cells with immune splenocytes obtained after sequential primary and memory immunization (9, 13, 14). In order to directly compare the effect of altering D H locus content in the same classic context, we generated anti-phOx mAb-secreting hybridomas from immune splenocytes harvested after primary, secondary, and tertiary immunizations of D-altered ΔD-DμFS and ΔD-iD mutant mice.…”

Section: Resultsmentioning

confidence: 99%

“…In BALB/c mice, IgM mAb (black bars) were only prepared early after primary immunization; see also legend to Figure 1. Data for IgG (white bars) are taken from two previous publications (9, 10). V H and V L variability is indicated for anti-phOx mAb of BALB/c wild-type mice (A,D) , ΔD-DμFS mice (B,E) , and ΔD-iD mice (C,F) .…”

Section: Resultsmentioning

confidence: 99%

“…(G–I) Expression of Ox1-idiotypic gene combination VH171/Vκ072 by monoclonal anti-phOx Ab from the TD response in BALB/c wild-type mice (G) , ΔD-DμFS mice (H) , and ΔD-iD mice (I) . Data of BALB/c wild-type mice are taken from previous publications (5, 9, 10). …”

Section: Resultsmentioning

confidence: 99%

“…BALB/c WT and D-altered ΔD-DμFS and ΔD-iD mice were immunized with the TD hapten–protein complex phOx-coupled chicken serum albumin (phOx-CSA) (molar ratio ~11) (9, 10). At 3–4 months of age, animals of all three strains received 80 μg of phOx-CSA adsorbed to Al(OH) 3 as a primary intraperitoneal immunization.…”

Section: Methodsmentioning

confidence: 99%

“…The relative affinities of mAb antibodies to phOx were determined with a hapten-inhibition test as previously described (9). These affinities were assessed in comparison to that of two prototypic Ox1-idiotypic mAb: H11.5 (μ,κ) for IgM and NQ2/16.2 (γ,κ) for IgG Ab.…”

Section: Methodsmentioning

confidence: 99%

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Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

et al. 2014

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The diversity of the third complementarity determining region of the IgH chain is constrained by natural selection of immunoglobulin diversity (DH) sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD) immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA). We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb) from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching, and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered ΔD-DμFS and ΔD-iD strains were significantly reduced. An increased prevalence of IgM-producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR) or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype, which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion, as well as CSR indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

et al. 2014

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Immunoglobulin class switching appears to be regulated by B‐cell antigen receptor‐specific T‐cell action

et al. 2012

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Summary Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T cell-dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2-phenyloxazolone (phOx) as well as those generated after phOx protein carrier-induced thymus-dependent or Ficoll-induced thymus independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during CSR exhibited a reduced VH/VL repertoire that was enriched for variable domains with shorter and more uniform CDR-H3 lengths and almost completely stripped of variable domains encoded by the large VH1 family. Thus, contrary to the current paradigm, T-cell dependent clonal selection during CSR appeared to select for VH family and CDR-H3 loop content even when the affinity provided by alternative clones exhibited similar to increased affinity for antigen.

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Development of adaptive immune cells

La Cava

2024

The Rose and Mackay Textbook of Autoimmune Diseases

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Thymus-independent type 2 antigen induces a long-term IgG-related network memory

Cited by 6 publications

References 64 publications

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

Immunoglobulin class switching appears to be regulated by B‐cell antigen receptor‐specific T‐cell action

Development of adaptive immune cells

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