ANTIGEN-SPECIFIC B CELL IMMUNITY
| Clonal Evolution in B Cell Immunity. |
 Click image to enlarge |
The rapid evolution of B cell memory occurs at the cellular level and is controlled by multiple cognate checkpoints during the development of adaptive immunity. While clonal selection is the fundamental process that underpins adaptive immunity, still surprisingly little is understood about the mechanism of its action across multiple junctures of antigen-specific memory B cell development in vivo.
|
| Memory B Cell Development. |
 Click image to enlarge
|
Recognition of native antigen by naïve B cells is the earliest developmental checkpoint and together with cognate T cell help, determines whether antigen-responsive B cells become short-lived plasma cells or enter the germinal center pathway to memory B cell development. In the germinal center cycle of events, antigen-specific B cells expand, diversify their BCR and are positively selected into the memory B cell compartment. The regulation of these events by antigen and germinal center Th cells remain poorly understood and is a major focus of our current research.
|
| Consolidation of B Cell Memory. |
 Click image to enlarge
|
Protein vaccination requires boosting with secondary antigen re-challenge. The control of the boost response is not a simple recapitulation of the events that establish the memory compartment after initial priming. Memory Th cells regulate memory B cell responses in ways that re-shape the cellular and humoral compartments of long-term immunity.
|
Plasma Cell Development. There are multiple subtypes of antibody producing plasma cells that vary according to their longevity, life histories, growth and niche requirements as well as the antibody isotype they secrete. High affinity antibody is still considered the best first line of defense in long-term immune protection.
These studies will define the dynamics of clonal evolution in the memory B cell compartment. Our preliminary studies in both the antigen-specific Th cell and memory B cell compartments suggest that the strength of antigen binding impacts cell fate determination. Using established methodologies and new animal models, we will dissect the mechanisms that control BCR repertoire selection at each checkpoint during antigen-specific effector and memory B cell development after initial priming and upon antigen recall. Over the course of these studies, we will also provide new ways to evaluate the efficacy of protein vaccination and help to define the best means for obtaining high affinity B cell memory in vivo.
KEY PUBLICATIONS
• McHeyzer-Williams, M.G., Nossal, G.J.V., Lalor, P.A. (1991) Molecular characterization of single memory B cells. Nature. 350:502. PubMed Abstract
• McHeyzer-Williams, L.J., Cool, M., McHeyzer-Williams, M.G. (2000). Antigen-specific B cell memory: expression and replenishment of a novel B220- memory B cell compartment. J. Exp. Med. 191:1149-1165.
PubMed Abstract
• Shapiro-Shelef, M.A., Lin, K-I., McHeyzer-Williams, L.J., Liao, J., McHeyzer-Williams, M.G. and Calame, K. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. (2003) Immunity 19:607-620. PubMed Abstract
• McHeyzer-Williams, L.J. and McHeyzer-Williams, M.G. Antigen-Specific Memory B Cell Development. (2005) Annual Reviews Immunol. Vol.23:487-513. PubMed Abstract
| RESEARCH AREA |
|
1. Antigen-experienced Dendritic Cells more |
| 2. Antigen-specific Helper T Cell Immunity more |
|
| 4. Antigen-specific B Cell Immunity more |
|
