Mouse B cell activation is inhibited by CD44 cross-linking.
Lymphocyte activation and trafficking are indispensable to the immune system. CD44 is an adhesion molecule with known importance in T cell activation, lymphocyte trafficking, and tumor metastasis. Although CD44 has been shown to participate in the activation, rolling and adhesion, and homing of T cells, the role of CD44 on B cells is relatively unknown. The effects of CD44 cross-linking on murine B cell activation via CD40L was explored using the anti-CD44 mAbs RK3G9 and IM7. When immobilized on a plate, both RK3G9 and IM7 were found to strongly inhibit B cell proliferation and Ig production, especially at lower cell input concentrations. IgE inhibition was especially prominent. In contrast, soluble RK3G9 added to the B cell cultures had no effect. The inhibitory effect of anti-CD44 on B cell activation was not influenced by the addition of the anti-FcgammaRII, indicating that Fc cross-linking did not play a role in this inhibition. As Ig production requires several days for both B cell proliferation and differentiation to occur, the effects of delayed addition of immobilized anti-CD44 mAbs were studied, and the results indicated no inhibition after 96 hrs of culture. Finally, B cells were activated by either LPS or anti-IgM F(ab')2. While LPS-induced B cell activation was inhibited by immobilized anti-CD44 mAbs, anti-IgM activation was refractory. Interestingly, addition of both anti-IgM and CD40L or LPS resulted in some modulation of the inhibitory activity. These results suggest that CD44 cross-linking could control polyclonal B cell activation by CD40L, but allow sIgM/CD40L activation to continue.
Wyant
Tiana L
TL
Virginia Commonwealth University/MCV, Richmond, VA 23298, USA. tlurgoli@hsc.vcu.edu
Fisher
Michael T
MT
McKallip
Robert J
RJ
Nagarkatti
Prakash S
PS
Nagarkatti
Mitzi
M
Conrad
Daniel H
DH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D018960:Hyaluronan Receptors; D007136:Immunoglobulins; D017452:Receptors, IgG; D023201:CD40 Ligand