Ig heavy chain promotes mature B cell survival in the absence of light chain.
Survival of mature B cells is thought to depend on the BCR signaling (BCR) because ablation of either H chain (HC) expression or BCR signaling causes B cells to rapidly disappear. Whether a complete BCR is required for survival of mature B cells is not known. To address this question, we generated a mouse in which we can repress the expression of a transgenic Ig L chain (IgL) by doxycycline (IgL-repressible mouse). Repression of IgL abrogated expression. Surprisingly, however, IgL-negative B cells survived longer than 14 wk, expressed signal-competent HC on the cell's surface, and active unfolded protein response factors. Like postgerminal center B cells, IgL-negative B cells were small lymphocytes, not dividing and expressed Bcl-6. Our results indicate that expression of unpaired HC, as it may occur as a consequence of Ag ligation, somatic hypermutation, or receptor editing, facilitates the survival of cells either by inducing receptor signaling or by inducing unfolded protein response and/or the expression of survival genes such as Bcl-6.
Geraldes
Pedro
P
Transplantation Biology Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Rebrovich
Michelle
M
Herrmann
Kai
K
Wong
Jamie
J
Jäck
Hans-Martin
HM
Wabl
Matthias
M
Cascalho
Marilia
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004318:Doxycycline / Q000008:administration & dosage; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000502:physiology*; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007148:Immunoglobulin mu-Chains; D007166:Immunosuppressive Agents; D011947:Receptors, Antigen, B-Cell; D004318:Doxycycline