The allogeneic T and B cell response is strongly dependent on complement components C3 and C4

Area of Science:

• Immunology
• Transplantation Biology
• Complement System

Background:

• Antibody production against histocompatibility antigens is critical for organ transplant success.
• Understanding the mechanisms controlling these antibody responses is essential.

Purpose of the Study:

• To investigate the role of the complement system in the immune response to allogeneic stimulation.
• To dissect the functions of the alternative, classical, and terminal complement pathways in alloimmunity.

Main Methods:

• Utilized mice deficient in complement components C3, C4, and C5.
• Administered fully major histocompatibility complex disparate skin grafts.
• Assessed allospecific immunoglobulin G and M responses, IgG isotype repertoire, and T cell functions (proliferation, interferon-gamma secretion).

Main Results:

• Allospecific IgG response was significantly impaired in C3- and C4-deficient mice, but not C5-deficient mice, especially in second-set responses.
• C3-deficient mice showed a reduced range of IgG isotypes and impaired T cell proliferation and interferon-gamma secretion.
• No impairment of the allospecific IgM response was observed in complement-deficient mice.

Conclusions:

• Defective complement activation impairs both T and B cell functions in alloimmune responses.
• The classical complement pathway plays a predominant role in stimulating alloimmunity, while the terminal pathway appears less important.
• These findings have significant implications for preventing sensitization in transplant recipients.