The antiphospholipid syndrome as a model for B cell-induced autoimmune diseases

Thromb Res. 2004;114(5-6):363-9. doi: 10.1016/j.thromres.2004.06.019.


Growing awareness of the pathophysiological importance of B cells for antiphospholipid antibody syndrome (APS), particularly those expressing the T cell marker CD5, has recently led to the proposal that their tolerance may be used as a method to reduce specific antibody (Ab) production. B cell tolerance has indeed become one of the most exciting developments in the treatment of this disease. Based on their production of multispecific Ab, these CD5+ B lymphocytes, also referred to as B-1 cells, are thought to account for most of the AutoAb in autoimmune murine models. Raised numbers of circulating CD5+ B cells correlate with high levels of anti-phospholipid (PL) Ab in some APS patients, and participate in altered immunity of women with recurrent spontaneous abortion. These findings are not surprising in view of the cross-reaction with PL of anti-bromelain-treated erythrocyte Ab secreted by these cells. Transgenic animals have, however, shown that B lymphocytes contribute to such disorders through a variety of characteristics other than Ab production. Indeed, owing to the role of the CD5 molecule in the maintenance of clonal anergy, increased proportions of B-1 cells may merely reflect their defective regulation through CD5 itself. Various B cell receptor (BCR)-associated transmembrane glycoproteins are also involved in the behavior of the cells. These include CD19 which amplifies the message, and CD22 which dampens down the BCR signaling. In addition, B lymphocytes may act as potent antigen-presenting cells for autoantigens, all the more because they secrete an excess of autocrine-acting interleukin-10 in autoimmune states. Furthermore, by modifying the specificity of their BCR, not only in the bone-marrow, but also in the secondary lymphoid organs, autoreactive B cells may initiate new immunoglobulin rearrangements. It is interesting that self-reactive Ab-making cells present with such rearrangements. Finally, B cells have the capacity to polarize into B effector (Be)-1 and Be-2, with different cytokine patterns that regulate the levels of T helper (Th)-1 and Th-2, respectively. Such a cytokine might be defective in nonorgan-specific autoimmune diseases. In conclusion, B lymphocytes are required for the initiation of anti-self Ab-associated disorders, such as APS. Their classical view in the biology of immune responses to self as autoAb secreting cells turns out to be rather naive, and an essential role for B lymphocytes may not be producing autoAb.

Publication types

  • Review

MeSH terms

  • Abortion, Habitual
  • Animals
  • Antigens, CD19 / biosynthesis
  • Antiphospholipid Syndrome / diagnosis*
  • Antiphospholipid Syndrome / pathology
  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / pathology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD5 Antigens / biosynthesis
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Erythrocytes / immunology
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Lymphocyte Activation
  • Male
  • Mice
  • Pregnancy
  • Signal Transduction


  • Antigens, CD19
  • CD5 Antigens
  • Cytokines
  • Glycoproteins