T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

Vinuesa, Carola G.; O'Leary, Paula; Sze, Daniel Man-Yuen; Toellner, Kai‐Michael; MacLennan, Ian C. M.

doi:10.1002/(sici)1521-4141(199904)29:04<1314::aid-immu1314>3.0.co;2-4

Cited by 104 publications

(41 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the initial response to T-dependent antigens [6], and in responses to thymus-independent type 2 antigens, it is the only pathway of productive B-cell differentiation and CSR [17]. We show here that AID induced by NP-Ficoll is expressed at lower levels than in GC blasts and is not coexpressed with Bcl6.…”

Section: Discussionmentioning

confidence: 69%

See 1 more Smart Citation

Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts

et al. 2011

Self Cite

View full text Add to dashboard Cite

Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B-cell blasts mature directly to plasmablasts without forming germinal centers. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues. The present study identifies the differentiation stage where CSR occurs in an extrafollicular response induced by 4-hydroxy-3-nitrophenyl acetyl (NP) conjugated to Ficoll (NP-Ficoll). To do this, we took advantage of the antigen dose dependency of CSR in this response. Thus, while both 30 and 1 lg NP-Ficoll induce plasmablasts, only the higher antigen dose induces CSR. Activation-induce cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP-specific B-cell blasts induced by 30 lg NP-Ficoll express AID. None of the B blasts responding to the non-CSR-inducing 1 lg dose of NP-Ficoll express AID. We confirmed that CSR occurs in B blasts by demonstrating the presence of rearranged heavy-chain transcripts in B blasts in the 30 lg response. CSR in this extrafollicular response is confined to B blasts, because NP-specific plasmablasts, identified by expressing CD138 and Blimp-1, no longer express AID and cannot undergo CSR.

show abstract

Section: Discussionmentioning

confidence: 69%

“…As in WT mice [17] NP-specific cells from QMxB6 mice move from the marginal zone and follicles to the T zone within 8 h of immunization with 30 mg NP-Ficoll (Fig. 1A, top two panels).…”

Section: Csr Occurs In B Blasts Rather Than Plasmablasts Responding Tmentioning

confidence: 77%

Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…For both classes of immunogen, increased Btk protein was found in a subpopulation (Ϸ10-15%) of B cells from wild-type mice (data not shown). Previous analysis of splenic lymphocyte responses to specific antigens suggests that a much smaller percentage of cells (Ͻ1%) is directly activated through antigen-receptor interactions (48). Thus, in vivo Btk up-regulation in T-dependent and -independent immune responses may reflect both direct and indirect effects of splenic lymphocyte activation.…”

Section: Resultsmentioning

confidence: 99%

Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells

Nisitani

Satterthwaite

Akashi

et al. 2000

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

View full text Add to dashboard Cite

Mutation of Bruton's tyrosine kinase (Btk) causes human X-linked agammaglobulinemia and murine X-linked immunodeficiency syndrome (xid). Quantitative aspects of B lymphocyte development and function have been demonstrated to depend on Btk level in vivo by using a murine transgenic model system. A sensitive intracellular immunofluorescent assay was developed to measure Btk protein on a per cell basis to test the hypothesis that its dosage is dynamically regulated during B cell development or functional responses. Marrow-derived hematopoietic stem cells, common lymphoid progenitor cells, and developing B and myeloid lineages expressed Btk protein at comparable levels. Resting peripheral B lineage cells had a significantly lower amount of Btk than marrow-derived cells in both wild-type and xid mice. Activation of the B cell antigen receptor up-regulated Btk protein level 10-fold within several hours by a phosphatidylinositol 3-kinase-dependent, posttranscriptional mechanism. In contrast, the protein level of Btk R28C in activated B lymphocytes from xid mice remained low. Bypass of the antigen receptor signaling pathways by treatment of cells with phorbol myristic acid and ionomycin rescued up-regulation of Btk protein in xid splenic B cells. These combined results suggest that certain receptor signals mediated by Btk regulate the level of expression of Btk protein in responding B lymphocytes to potentiate signal transduction. Dynamic regulation of Btk protein dosage is an additional mechanism to modulate B lymphocyte immune functions.

show abstract

“…The results indicated that the fate of a B cell was determined during an early time window after antigen encounter. In the absence of supply of naive B cells from the bone marrow, a high antigen-to-B cell ratio resulted in terminal differentiation of LCMV-nAb-producing B cells into IgM AFC, which have been shown to have a short life span [16]. Similarly, B cells confronted with antigen in the absence of T cell help terminally differentiated into IgMproducing cells.…”

Section: Discussionmentioning

confidence: 99%

Parameters governing exhaustion of rare T cell‐independent neutralizing IgM‐producing B cells after LCMV infection

et al. 2006

View full text Add to dashboard Cite

The late appearance of neutralizing antibodies (nAb) against lymphocytic choriomeningitis virus (LCMV) has been attributed to various factors including immunopathology, low frequency of high-affinity specific B cells and competition by nonspecific polyclonal B cell activation. To investigate the activation of LCMV-nAb-producing B cells early following infection, we performed adoptive transfers of LCMV-specific B cells into WT recipients. By modulating parameters such as viral load, number of specific B cells and presence of T cell help, we found that a high antigen-to-B cell ratio led to normal IgM responses. IgG and memory responses, however, were impaired as most nAbproducing B cells rapidly terminally differentiated into short-lived IgM plasma cells. Lowering the antigen-to-B cell ratio, or increasing the level of T cell help, could rescue the class-switched antibody response. Upon infection, a low frequency of LCMV-nAbproducing B cells, as observed in WT mice, results in a high antigen-to-B cell ratio and is likely to lead to terminal differentiation -and elimination -of these rare B cells.

show abstract

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

Cited by 104 publications

References 34 publications

Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts

Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts

Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells

Parameters governing exhaustion of rare T cell‐independent neutralizing IgM‐producing B cells after LCMV infection

Contact Info

Product

Resources

About