Trends in Immunology
Volume 32, Issue 2, February 2011, Pages 80-88
Journal home page for Trends in Immunology

Review
To B or not to B: B cells and the Th2-type immune response to helminths

https://doi.org/10.1016/j.it.2010.11.005Get rights and content

Similar T helper (Th)2-type immune responses are generated against different helminth parasites, but the mechanisms that initiate Th2 immunity, and the specific immune components that mediate protection against these parasites, can vary greatly. B cells are increasingly recognized as important during the Th2-type immune response to helminths, and B cell activation might be a target for effective vaccine development. Antibody production is a function of B cells during helminth infection and understanding how polyclonal and antigen-specific antibodies contribute should provide important insights into how protective immunity develops. In addition, B cells might also contribute to the host response against helminths through antibody-independent functions including, antigen presentation, as well as regulatory and effector activity. In this review, we examine the role of B cells during Th2-type immune response to these multicellular parasites.

Section snippets

Helminths and the host response

Chronic infection with helminth parasites has a significant impact on global health; more than 2 billion people worldwide are infected, and these parasites can cause high morbidity including malnourishment and anemia. Although drug treatments do exist, reinfection can occur after treatment; typically in parasite endemic areas, and drug resistance is also becoming an issue. As such, the development of effective vaccines against helminths would be a major advance for control and treatment of

Vaccination against helminths

Current strategies to control helminth-related morbidity involve regular and mass drug administration, integrated with disease control through improved sanitation and hygiene [2]. Although safe and effective drugs are currently available for the bulk of human parasitic helminth infections, rapid reinfection and the dramatic rise in drug-resistant helminths of veterinary importance have raised concerns over the feasibility of drug administration as a long-term control strategy [2]. Yet, there is

A protective role for antibodies?

During helminth infection, polarized Th2-type responses promote B cell class switching to IgE and IgG1. Interleukin (IL)-4 receptor signaling and cognate T–B cell interactions mediate production of both isotypes. IgE potently activates mast cells and basophils, on which, antigen crosslinks Fc epsilon Receptor 1 (FcɛRI)-bound IgE to trigger degranulation and release of soluble mediators from these cells (Figure 1). IgE does not play an essential role in protective immunity against

Helminth-induced production of polyclonal antibodies: help or hindrance?

Helminth infection has long been associated with the marked production of polyclonal IgE antibodies. Formal proof that helminth infection can lead to the production of irrelevant antibody specificities has been provided by H. polygyrus bakeri infection of TgH(VI10)xYEN mice [8]. Almost all B cells in these mice express a neutralizing immunoglobulin against the vesicular stomatitis virus glycoprotein (VSV-GP). In these mice, the immunoglobulin heavy chain locus can undergo class switch

Do B cells enhance Th2-type responses

B cells have several important activities in addition to antibody production, including antigen presentation, co-stimulatory molecule signaling, and cytokine production. However, the importance of B cells in driving a T cell-dependent response can vary with the particular antigen and the type of immune microenvironment. In draining lymph nodes, antigen-presenting DCs first interact with naïve T cells in the T zone, and activated T cells then migrate to the B zone 60, 61. In the T:B zone [62],

Helminth-induced regulatory B cells

Immune regulation by B cells was first recognized for autoimmune conditions (Box 2). Regulatory B cells also play a role during helminth infection. B cell deficiency results in enhanced Th2-dependent immunopathology following experimental S. mansoni infection. A similar increase in immune pathology is observed in mice deficient for FcγRs, which indicates a complex relationship between antibody secretion and B cell function in this model [74]. Regulatory B cells also play a role during

Concluding remarks

It is clear that B cells are important in protective immunity against helminths. However, their significance and function can differ greatly depending on the specific parasite. During mucosal responses to helminths, where B cells are essential for protective immunity, antibody secretion appears most significant, and exogenous antibody administration can largely substitute for B cell deficiency. Other helminths elicit host protective responses in the absence of B cells, although even in these

Acknowledgments

N.Harris is supported by the Swiss Vaccine Research Institute. W.C. Gause is supported by NIH grants R01AI66188, R01AI031678, and R01AI069395.

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