Toll-like receptor agonists synergize with CD40L to induce either proliferation or plasma cell differentiation of mouse B cells.

In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive immune cells. However, recent data showed that TLRs (Toll Like Receptors), the most characterized class of Pattern Recognition Receptors, are also expressed by adaptive immune B cells. B cells play an important role in protective immunity essentially by differentiating into antibody-secreting cells (ASC). This differentiation requires at least two signals: the recognition of an antigen by the B cell specific receptor (BCR) and a T cell co-stimulatory signal provided mainly by CD154/CD40L acting on CD40. In order to better understand interactions of innate and adaptive B cell stimulatory signals, we evaluated the outcome of combinations of TLRs, BCR and/or CD40 stimulation. For this purpose, mouse spleen B cells were activated with synthetic TLR agonists, recombinant mouse CD40L and agonist anti-BCR antibodies. As expected, TLR agonists induced mouse B cell proliferation and activation or differentiation into ASC. Interestingly, addition of CD40 signal to TLR agonists stimulated either B cell proliferation and activation (TLR3, TLR4, and TLR9) or differentiation into ASC (TLR1/2, TLR2/6, TLR4 and TLR7). Addition of a BCR signal to CD40L and either TLR3 or TLR9 agonists did not induce differentiation into ASC, which could be interpreted as an entrance into the memory pathway. In conclusion, our results suggest that PAMPs synergize with signals from adaptive immunity to regulate B lymphocyte fate during humoral immune response.

An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2.

In conditions of T lymphopenia, interleukin (IL) 7 levels rise and, via T cell receptor for antigen-self-major histocompatibility complex (MHC) interaction, induce residual naive T cells to proliferate. This pattern of lymphopenia-induced "homeostatic" proliferation is typically quite slow and causes a gradual increase in total T cell numbers and differentiation into cells with features of memory cells. In contrast, we describe a novel form of homeostatic proliferation that occurs when naive T cells encounter raised levels of IL-2 and IL-15 in vivo. In this situation, CD8(+) T cells undergo massive expansion and rapid differentiation into effector cells, thus closely resembling the T cell response to foreign antigens. However, the responses induced by IL-2/IL-15 are not seen in MHC-deficient hosts, implying that the responses are driven by self-ligands. Hence, homeostatic proliferation of naive T cells can be either slow or fast, with the quality of the response to self being dictated by the particular cytokine (IL-7 vs. IL-2/IL-15) concerned. The relevance of the data to the gradual transition of naive T cells into memory-phenotype (MP) cells with age is discussed.

Improving Transition Outcomes: Introducing the Prototype Replication Templates

Brief overview of the three community demonstration prototypes established under Improving Transition Outcomes and an introduction to the Replication Templates developed to assist community teams.

Improving Transition Outcomes: Prototype First Year Highlights

Highlights from the community demonstration prototypes first year.

Improving Transition Outcomes: Prototype Work Plan Template

Work Plan template developed for the Improving Transition Outcomes community demonstration prototypes.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Training Brochure

Promotional brochure for CASE (Career And Self Awareness) curriculum trainings.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Community Team Award

Promotional article recognizing an award presented to the CASE (Career And Self Awareness) team.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Conference Presentation

Promotional article recognizing a CASE (Career And Self Awareness) conference presentation.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Iowa Association of Community Providers Award

Promotional article recognizing an award presented to the CASE (Career And Self Awareness) team.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Success Stories

Success Stories from the CASE (Career And Self Awareness) prototype.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: General Information

General information on the CASE (Career And Self Awareness) prototype.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Contact Information

Contact information for the CASE (Career And Self Awareness) prototype.

Improving Transition Outcomes: CASE (Career And Self Awareness) Prototype: Basic Points

Basic Points about the CASE (Career And Self Awareness) prototype.