Influenza virus hemagglutinin induces differentiation of mature resting B cells and growth arrest of immature WEHI-231 lymphoma cells

• Published in: The Journal of immunology (1950) Vol. 152; no. 11; pp. 5381 - 5391
• Main Authors: Rott, O, Cash, E
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.1994
• Subjects: Animals; B-Lymphocytes - drug effects; Cell Differentiation - drug effects; Cell Division - drug effects; Cytokines - pharmacology; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral - pharmacology; Immunoglobulins - biosynthesis; influenza virus; Leukocyte Common Antigens - physiology; Lipopolysaccharides - pharmacology; Lymphocyte Activation - drug effects; Lymphoma - pathology; Mice; Mice, Inbred BALB C; Receptors, Antigen, B-Cell - physiology; Tumor Cells, Cultured; Viral Envelope Proteins - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.152.11.5381

We have investigated the functional requirements for the B cell "mitogenicity" of the influenza virus hemagglutinin (HA). Murine B cell proliferative responses were inducible by either infectious or inactivated virus, and by infected, paraformaldehyde-fixed cells. Viruses of the 12 different HA-subtypes displayed marked differences in their activation potential, classifying them as high (H2, H4, H6, H12), medium (H3, H5, H8, H9), or low (H1, H7, H10, H11) B cell activators. HA-mediated proliferation of resting B cells induced a vigorous Ig synthesis, with a predominance of IgG2b, IgG3, and IgM production. In this activation mode the B cell receptor (BCR) complex seems to be involved because 1) virus-triggered B cell proliferation was blocked by anti-Ig Abs, 2) B cell responses could be competitively inhibited by unfractionated high dose Igs, and 3) addition of BCR-modulating anti-CD45 mAb abrogated subsequent stimulation by HA. Furthermore, 4) influenza viruses were able to induce a growth arrest in the anti-mu sensitive B cell line WEHI-231. Most interestingly, the "tolerogenic" capacity correlated with the B cell stimulatory subtype of the virus, because highly stimulatory HA-subtypes were highly "tolerogenic" whereas low stimulatory subtypes were only marginally effective. Collectively, these observations raise the hypothesis that influenza viruses can cause polyclonal proliferation/differentiation of mature B cells and inactivation/tolerance induction in immature B cells by a mechanism that seems to mimic certain aspects of the physiologic BCR complex-mediated B cell activation.